Growth factors are naturally occurring proteins or peptides that play a significant role in regulating cellular growth, proliferation, and differentiation in horses. These factors are involved in various physiological processes, including tissue repair, development, and immune function. Common growth factors studied in equine research include insulin-like growth factor (IGF), transforming growth factor-beta (TGF-β), and fibroblast growth factor (FGF). Their expression and activity can influence wound healing, musculoskeletal development, and recovery from injury. This page compiles peer-reviewed research studies and scholarly articles that examine the role, regulation, and clinical significance of growth factors in equine biology and health.
Silva ESM, Cuervo-Arango J, de Ruijter-Villani M, Klose K, Oquendo PS, Stout TAE.Field data indicate that a longer period of estrus prior to ovulation correlates positively with fertility. To test the hypothesis that the duration of exposure to estrogens prior to progesterone dominance influences endometrial function, we used anestrous mares to simulate varying durations of estrus (3 groups of 5 mares): long (LE), short (SE), and no estrus (NE), as determined by the duration of estradiol priming prior to progesterone treatment: 7, 2 and 0 days for the LE, SE and NE, respectively. Endometrial biopsies were recovered 4 days after progesterone administration in all groups for...
Lasarzik de Ascurra J, Ehrle A, Einspanier R, Lischer C.Autologous conditioned serum (ACS) is commonly used for the treatment of human and equine osteoarthritis (OA). The objective of this study was to investigate the influence of incubation time and incubation tube on concentrations of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 beta (IL-1β), and insulin-like growth factor-1 (IGF-1) in ACS of horses with and without OA. Blood samples of 7 control horses and 6 horses with naturally occurring OA were obtained. The concentration of serum IL-1ra, IL-1β, and IGF-1 was determined after 12, 24, and 36 hours of incubation using commercial ...
Bonometti S, Menarim BC, Reinholt BM, Ealy AD, Johnson SE. To provide insight into maternal recognition of pregnancy control in equids, the mitogenic and developmental effects of endometrium-expressed growth factors (epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1)) were examined in equine iTr cells, an equine trophectoderm cell line. Initial western blots revealed that HGF and IGF-1 stimulate phosphorylation of AKT serine/threonine kinase 1 (AKT1) and EGF, FGF2, or HGF resulted in phosphorylation of both extracellular signal-regulated kinase 1 (ERK1) and ERK2...
Viganò M, Tessaro I, Trovato L, Colombini A, Scala M, Magi A, Toto A, Peretti G, de Girolamo L.The management of cartilage lesions is an open issue in clinical practice, and regenerative medicine represents a promising approach, including the use of autologous micrografts whose efficacy was already tested in different clinical settings. The aim of this study was to characterize in vitro the effect of autologous cartilage micrografts on chondrocyte viability and differentiation and perform an evaluation of their application in racehorses affected by joint diseases. Methods: Matched human chondrocytes and micrografts were obtained from articular cartilage using Rigenera® procedure. Chond...
Kwirant LADA, De La Corte FD, Cantarelli C, Cargnelutti JF, Martins M, Cabral MW, Maciel N, Rubin MIB.Equine platelet-rich plasma (PRP) has been used in horses to repair bone, articular and tendinous lesions, laminitis, and even endometritis. However, platelets have a very limited lifespan, which makes it difficult to prepare and use PRP, except in loco. With the aim to produce PRP with higher platelet viability for clinical purposes, the effects of the cryoprotectants dimethyl sulfoxide (DMSO) and trehalose were evaluated on cooled (4°C) and cryopreserved (-196°C) equine PRP. The protocols of cooling and cryopreservation were performed independently, comparing the following treatments: fres...
Max MC, Bizarro-Silva C, Búfalo I, González SM, Lindquist AG, Gomes RG, Barreiros TRR, Lisboa LA, Morotti F, Seneda MM.Folliculogenesis is a process of development and maturation of the ovarian follicles, being essential for the maintenance of fertility. In in vivo conditions, 99.9% of the follicles of an ovary do not ovulate and undergo atresia. In order to minimize this loss and to clarify the existing mechanisms, a technique was developed that allows for the in vitro follicular development. The objective of this study was to evaluate the effects of different epidermal growth factor (EGF) concentrations on the in vitro culturing of equine preantral follicles. Ovaries (n = 10) were collected from a local ...
Scaravaggi I, Borel N, Romer R, Imboden I, Ulbrich SE, Zeng S, Bollwein H, Bauersachs S.Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showe...
Roth SP, Schubert S, Scheibe P, Groß C, Brehm W, Burk J.Age-related degenerative changes in tendon tissue represent a common cause for acute tendon pathologies. Although the regenerative potential of multipotent mesenchymal stromal cells (MSC) was reported to restore functionality in injured tendon tissue, cellular mechanisms of action remain partly unclear. Potential tenogenic differentiation of applied MSC is affected by various intrinsic and extrinsic factors. The current study presents an in vitro model to evaluate the combined extrinsic effects of decellularized equine tendon matrix, transforming growth factor beta 3 (TGFβ3) and bone morphoge...
Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J.Horses afflicted with degenerative suspensory ligament desmitis (DSLD) suffer from progressive leg pain and lameness without history of trauma. DSLD is a systemic disorder caused by abnormal accumulation of proteoglycans in many connective tissues. One proteoglycan found in higher quantities in DSLD is decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan chain in DSLD. In addition to acellular accumulations of proteoglycans foci of active fibroblasts/tenoblasts were observed in some tendons and suspensory ligaments (SLs) from DSLD cases We have hypothesized that th...
Gurusinghe S, Bandara N, Hilbert B, Trope G, Wang L, Strappe P.Monolayer expansion of chondrocytes in culture results in the dedifferentiation of chondrocytes with inferior cartilage specific extracellular matrix synthesis and proliferation when compared with its native counterpart. We aimed to enhance chondrocyte proliferation and articular cartilage specific gene expression through ectopic expression of the major pluripotency transcription factors (Oct4, Sox2, Klf4 and c-Myc). We also aimed to provide insights to the modulation of TGFβ receptor mRNA with Klf4 overexpression. Equine chondrocytes pooled from three donors were transduced with lentiviral v...
Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA.This clinical study describes the intralesional application of the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor (VEGF164) and fibroblast growth factor 2 (FGF2) in seven horses to restore naturally occurring injuries of the superficial digital flexor tendon (SDFT) (tendinitis) and in three horses with suspensory ligament branch desmitis. Following application all horses were able to commence a more rapid exercise program in comparison to standardized exercise programs. Clinical observation and ultrasonic imaging was used to evaluate th...
Conrad S, Weber K, Walliser U, Geburek F, Skutella T.In adults the healing tendon generates fibrovascular scar tissue and recovers never histologically, mechanically, and functionally which leads to chronic and to degenerative diseases. In this review, the processes and mechanisms of tendon development and fetal regeneration in comparison to adult defect repair and degeneration are discussed in relation to regenerative therapeutic options. We focused on the application of stem cells, growth factors, transcription factors, and gene therapy in tendon injury therapies in order to intervene the scarring process and to induce functional regeneration ...
Ongchai S, Somnoo O, Kongdang P, Peansukmanee S, Tangyuenyong S.We investigated the effect of transforming growth factor beta 1 (TGF-β1) on equine hyaluronan synthase 2 () gene expression and hyaluronan (HA) synthesis in culture models of articular chondrocytes. Equine chondrocytes were treated with TGF-β1 at different concentrations and times in monolayer cultures. In three-dimensional cultures, chondrocyte-seeded gelatin scaffolds were cultured in chondrogenic media containing 10 ng/mL of TGF-β1. The amounts of HA in conditioned media and in scaffolds were determined by enzyme-linked immunosorbent assays. mRNA expression was analyzed by semi-quantita...
Brandt AM, Kania JM, Gonzalez ML, Johnson SE.Hepatocyte growth factor (HGF) signals mediate mouse skeletal muscle stem cell, or satellite cell (SC), reentry into the cell cycle and myoblast proliferation. Because the athletic horse experiences exercise-induced muscle damage, the objective of the experiment was to determine the effect of HGF on equine SC (eqSC) bioactivity. Fresh isolates of adult eqSC were incubated with increasing concentrations of HGF and the initial time to DNA synthesis was measured. Media supplementation with HGF did not shorten (P > 0.05) the duration of G0/G1 transition suggesting the growth factor does not aff...
da Silva Inácio DF, de Rezende ASC, Melo MM, Quintão Lana ÂM, Prado Silva RH, de Jesus Mendes L, de Paula Gonçalves Reis L, Maruch S, Ralston SL.Young horses reach nearly 90% of their final height in the first year of life. However, to achieve their genetic potential, it is necessary to receive adequate nutrition during this period of rapid growth. The objective of this study was to evaluate the effect of supplementation of sorghum silage during a period of limited pasture forage availability, on the body development, and health of Mangalarga Marchador (MM) weanling fillies. Fourteen healthy MM 6-month-old fillies were randomly assigned to one of two groups: GS (consuming silage) and GH (consuming grass hay (Cynodon spp) in addition to...
Ströbel C, Günther E, Romanowski K, Büsing K, Urubschurov V, Zeyner A.Foal first diarrhoea is one of the most prominent problems in the early life of horses. Probiotics might have the potency to prevent or at least diminish neonatal diarrhoea. We hypothesised that the treatment of foals with probiotic strains of Lactobacillus rhamnosus and Enterococcus faecium starting early after birth and then daily over 2 weeks would prevent or mitigate foal heat diarrhoea. The influence of this probiotic treatment on diarrhoea incidence and growth and health performance of young foals was investigated. Thirty-four foals were randomly allocated to two groups. From day 1 to 1...
Davis KA, Klohonatz KM, Mora DSO, Twenter HM, Graham PE, Pinedo P, Eckery DC, Bruemmer JE.Currently there is no contraceptive vaccine that can cause permanent sterility in mares. This study investigates the effect of vaccination against oocyte-specific growth factors, Bone Morphogenetic Protein 15 (BMP-15) and Growth Differentiation Factor 9 (GDF-9), on ovarian function of mares. It was hypothesized that immunization against these growth factors would prevent ovulation and/or accelerate depletion of the oocyte reserve. For this study, 30 mares were randomly assigned to three groups (n = 10/group) and vaccinated with BMP-15 or GDF-9 peptides conjugated to KLH and adjuvant, or a ...
Branly T, Contentin R, Desancé M, Jacquel T, Bertoni L, Jacquet S, Mallein-Gerin F, Denoix JM, Audigié F, Demoor M, Galéra P.Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that...
Robles M, Dubois C, Gautier C, Dahirel M, Guenon I, Bouraima-Lelong H, Viguié C, Wimel L, Couturier-Tarrade A, Chavatte-Palmer P.Primiparous mares are known to produce smaller foals than multiparous mares. This difference seems to be partly explained by the reduced exchange surface and volume of the placental villi in primiparous compared to multiparous placentas. The effect of maternal parity on foals' post-natal growth, metabolism and sexual maturation, however, has been given little consideration. The objectives of this work were to analyse placental biometry and structure at term, growth of foals and yearlings, their metabolism and testicular maturation at one year of age. Twenty multiparous mares (M), aged over 6 y...
Seabaugh KA, Thoresen M, Giguère S.Extracorporeal shockwave therapy (ESWT) and platelet-rich plasma (PRP) are common treatments for soft tissue injuries in horses. Shockwave triggers cell specific responses to promote healing. Growth factors released from PRP also promote healing. It has been hypothesized that greater growth factor release would amplify the healing process. The combination of ESWT and PRP could promote healing in injured tendons and ligaments in the horse. The objective of this study was to determine if application of shockwaves to PRP samples increases the concentration of transforming growth factor-β1 (TGF-...
Rushton JO, Kammergruber E, Tichy A, Egerbacher M, Nell B, Gabner S.Despite advances in therapy of corneal ulcerative diseases in horses, a vast number of cases require surgical intervention, due to poor response to treatment. Topical application of serum has been used for many years, based on its anticollagenolytic properties and the presence of growth factors promoting corneal wound healing. However, although other blood derived products i.e. platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely used in equine orthopaedics and in human ophthalmology, no reports of the effects of these blood derived products exist in equine ophthal...
Lee JY, Na HJ, Kim HM, Lee SC, Lee JY, Chung CP, Seol YJ, Park YJ.The purpose of this study was to evaluate the efficacy and safety of equine-derived bone matrix as a carrier for recombinant human platelet-derived growth factor BB (rhPDGF-BB) versus beta-tricalcium phosphate (β-TCP) for the treatment of intraosseous periodontal defects in adult patients. This study was performed on 32 adults with advanced periodontal disease. Eligible subjects were randomized in 1:1 ratio into a test (rhPDGF-BB-coated equine-derived bone matrix) or control group (rhPDGF-BB-coated β-TCP). Probing pocket depth (PD), clinical attachment level (CAL), gingival recession (GR), a...
Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA.In this clinical study, for the first time we used the direct gene therapy to restore severe injuries of the suspensory ligament branch and superficial digital flexor tendon in horses (). We injected the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor 164 and fibroblast growth factor 2 at the site of injury in the suspensory ligament branch and tendon. Treatment effects were evaluated with the use of clinical observation and ultrasound imaging during a period of a few months. We showed that gene therapy used within a period of 2-3 mont...
Jiménez-Aristizabal RF, López C, Álvarez ME, Giraldo C, Prades M, Carmona JU.To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β1) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs...
Berglund AK, Fisher MB, Cameron KA, Poole EJ, Schnabel LV.Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Effective and safe allogeneic therapy may be hindered, however, by recipient immune recognition and rejection of major histocompatibility complex (MHC)-mismatched MSCs. Development of strategies to prevent immune rejection of MHC-mismatched MSCs in vivo is necessary to enhance cell survival and potentially increase the efficacy and safety of allogeneic MSC therapy. The purposes of this study were to evaluate if transforming growth factor-β2 (TGF-β2) downregulated MHC expressi...
Sherman AB, Gilger BC, Berglund AK, Schnabel LV.We aimed to determine and compare the in vitro effects of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) and mesenchymal stem cell supernatant (MSC-Sp) on the wound healing capacity of equine corneal fibroblasts using a scratch assay. Bone marrow aspirates and eyes were collected from normal, euthanized horses with subsequent isolation and culture of BM-MSCs and corneal stromal cells. Corneal stromal cells were culture-expanded in the culture well of transwell plates and then treated with an autologous BM-MSC suspension (dose: 2.5 × 105/100 μL media with the BM-MSCs con...
Ropka-Molik K, Stefaniuk-Szmukier M, Z Ukowski K, Piórkowska K, Bugno-Poniewierska M.It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T (untrained horses), T (horses after intense gallop phase), and T (horses at the end of racing season), 23 samples in total. The numerous groups of exercise-...
Sumner SM, Naskou MC, Thoresen M, Copland I, Peroni JF.Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses. Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and co...
Beythien E, Aurich C, Wulf M, Aurich J.Seasonal changes in metabolic rate have been shown in horses and we hypothesized that this leads to the birth of smaller foals early in the year. Mares and their foals were assigned to three groups by day of foaling within the year (e.g. 1 January = day 1): Group 1 (n = 10) day 40-65, group 2 (n = 8) day 67-92, group 3 (n = 9) day 94-121. Groups did not differ with regard to parity. In foals, height at withers and body weight were determined on days 1-5 and weekly until 12 weeks of age. Chest circumference, distances fetlock to carpus, carpus to elbow, poll to nose and crown-rump lengt...
Baskerville CL, Bamford NJ, Harris PA, Bailey SR.Insulin-like growth factor-1 (IGF-1) plays several important physiological roles, and IGF-related pathways have been implicated in developmental osteochondral disease and endocrinopathic laminitis. This factor is also a downstream marker of growth hormone activity and its peptide mimetics. Unfortunately, previously used assays for measuring equine IGF-1 (radioimmunoassays and ELISAs) are no longer commercially available, and many of the kits on the market give poor results when used on horse samples. The aim of the present study was to compare three different ELISA assays (two human and one ho...
Bembo F, Eraud J, Philandrianos C, Bertrand B, Silvestre A, Veran J, Sabatier F, Magalon G, Magalon J.To assess the safety and potential efficacy of a standardized technique consisting of intra-articular injection of 10 cc of a homogeneous mixed product using autologous micro-fat and platelet rich plasma (PRP) (ratio 1:1) in the carpus or the fetlock joint of sport horses presenting degenerative joint disease (DJD). Methods: Eight sport horses with DJD confirmed by radiography and ultrasonography and causing lameness and the impossibility to compete were treated. PRP was prepared after a double centrifugation whereas micro-fat was harvested and purified using a closed system. The two products ...
Henson FM, Getgood AM, Caborn DM, McIlwraith CW, Rushton N.To investigate effects of 1% hyaluronic acid-chondroitin sulfate-N-acetyl glucosamine (HCNAG) on the damage repair response in equine articular cartilage. Methods: Articular cartilage from 9 clinically normal adult horses. Methods: Full-thickness cartilage disks were harvested from the third metacarpal bone. Cartilage was single-impact loaded (SIL) with 0.175 J at 0.7 m/s and cultured in DMEM plus 1 % (vol/vol) HCNAG or fibroblastic growth factor (FGF)-2 (50 ng/mL). Histologic and immunohistochemical techniques were used to identify tissue architecture and apoptotic cells and to immunolocalize...
Durgam SS, Stewart AA, Pondenis HC, Yates AC, Evans RB, Stewart MC.To compare in vitro expansion of equine tendon- and bone marrow-derived cells with fibroblast growth factor-2 (FGF-2) supplementation and sequential matrix synthesis with pulverized tendon and insulin-like growth factor-I (IGF-I). Methods: Cells from 6 young adult horses. Methods: Progenitor cells were expanded in monolayers with FGF-2, followed by culture with autogenous acellular pulverized tendon and IGF-I for 7 days. Initial cell isolation and subsequent monolayer proliferation were assessed. In pulverized tendon cultures, cell viability and expression of collagen types I and III and carti...
Hoskin SO, Gee EK.The feeding value of fresh pasture grazed in situ is determined by animal performance or productivity and could be relatively easily established for growing and lactating horses. Despite this, there is a lack of published information on the relative feeding value of different pastures and forages grazed by horses in New Zealand and the world. In addition, for adult breeding or non-breeding and young or adult sport or performance horses, the definition of feeding value and its determination remain problematic. Limited information suggests that the feeding value of perennial ryegrass-based pastu...
Strand E, Braathen LC, Hellsten MC, Huse-Olsen L, Bjornsdottir S.The Icelandic horse is a pristine breed of horse which has a pure gene pool established more than a thousand years ago, and is approximately the same size as living and extinct wild breeds of horses. This study was performed to compare the length of the skeletal growth period of the "primitive" Icelandic horse relative to that reported for large horse breeds developed over the recent centuries. This information would provide practical guidance to owners and veterinarians as to when the skeleton is mature enough to commence training, and would be potentially interesting to those scientists inve...
Sumner SM, Naskou MC, Thoresen M, Copland I, Peroni JF.Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses. Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and co...
Burling K, Seguin MA, Marsh P, Brinkman K, Madigan J, Thurmond M, Moon-Massat P, Mannis M, Murphy CJ.OBJECTIVE-To characterize healing of corneal epithelial defects in horses and to evaluate the ability of epidermal growth factor (EGF) to modulate rate of corneal epithelial healing in horses. Methods: 20 eyes in 12 adult horses. Methods: Corneal epithelial wounds were created by mechanically debriding the limbus. Corneal healing was recorded for 3 treatment groups: 50 microg of EGF/ml (n = 5 eyes), 5 microg of EGF/ml (7), and PBS solution (8). Corneal healing was recorded once daily after instillation of fluorescein stain by use of photography and calculating the area of the wound, using imag...
López C, Alvarez ME, Carmona JU.The aims were (1) to evaluate the bacteriostatic effect of platelet-rich plasma (PRP), platelet-rich gel (PRG), leukocyte-poor plasma (LPP), leukocyte-poor gel (LPG), plasma, and heat-inactivated plasma (IP) on both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) over a period of 24 h; (2) to determine and to compare the concentrations and degradation over time of platelet factor 4 (PF-4), transforming growth factor beta 1 (TGF-β 1), and platelet-derived growth factor isoform BB (PDGF-BB); and (3) to identify any correlations between...
Knottenbelt DC.Abstract Trunk/body wounds heal rapidly with prominent Contraction while wounds on the limb commonly fail to heal or heal slowly by centripetal epithelialization. often with insignificant contraction. Chronic exuberant granulating wounds on the limbs heal well after grafting from donor sites on the trunk. Indolent wounds are less common but may granulate significantly following moist wound-healing management. Sarcoid transformation is an increasingly important cause of healing failure. Sarcoid transformations on the trunk are commonly verrucose while those on the limb are usually aggressive...
Malinowski K, Christensen RA, Hafs HD, Scanes CG.A survey with horses was conducted to determine whether plasma concentrations of triiodothyronine (T3), thyroxine (T4), insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP) change as horses grow, mature sexually, and age. Jugular blood was sampled from Standardbred fillies and mares at ages 0, 1, 7, and 14 d, at 1, 2, 4, 5, 6, and 9 mo, and at 5 to 8 and 16 to 22 yr (n = 5 to 18). In a second survey, we measured the same variables in eight breeds of horses with markedly different adult body sizes, from Miniatures to Friesians. Plasma T3, T4, and IGF-I were determined by radioimm...
Fukuda K, Kuroda T, Tamura N, Mita H, Kasashima Y.Platelet-rich plasma (PRP) therapy has been widely applied in various medical fields including humans and horses. This study aimed to establish an optimal activation method to stably and reproducibly maximize the concentrations of platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) contained in equine PRP. Autologous PRP was prepared from 11 Thoroughbreds. For the activation test, PRP was activated by either a single freeze-thaw cycle (Fr) or adding calcium and autologous serum containing thrombin (Ca). PDGF-BB and TGF-β1 concentrations in Fr, Ca, nonactiv...
Sloet van Oldruitenborgh-Ooste , Mol JA, Barneveld A.Osteochondrosis (OC) is a multifactorial disorder with endocrinological dysfunction and mineral imbalance having a role in pathogenesis. The present study focused on a possible relationship between insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D (1,25(OH)2D), cortisol, copper, zinc, calcium, ionised calcium, magnesium and phosphorus and 5 different postmortem and radiographical osteochondrosis scores of hock and stifle joints in foals age 0-11 months. Osteochondrosis-positive foals showed a significantly lower IG...
De Angelis N, Scivetti M.This paper reports on a patient who underwent horizontal ridge augmentation using recombinant human platelet-derived growth factor BB (rhPDGF-BB) in combination with a collagenate equine block. Ninety days after the first surgery, 8 mm of new bone was noted on a computed tomography scan, and three 5-mm implants were placed. Histology, performed using confocal laser scanning microscopy, showed a large amount of newly formed bone well characterized with osteon and resorption lacunae, which demonstrated the intense bone remodeling. This study supports the use of rhPDGF-BB in combination with allo...
Lindbloom SM, Farmerie TA, Clay CM, Seidel GE, Carnevale EM.Human chorionic gonadotropin (hCG) was administered to mares in estrus with large, dominant ovarian follicles to initiate follicular and oocyte maturation. Follicular contents were collected at 0, 2, 4 and 6 h after hCG. Epiregulin, amphiregulin and phosphodiesterase (PDE) mRNA contents of granulosa cells (PDE 4D) were determined by reverse transcription and real-time PCR; PDE 3A mRNA content of single oocytes was determined similarly. Copy numbers of mRNA did not increase for PDE 3A or 4D over the time interval studied. Amounts of epiregulin and amphiregulin mRNA were correlated (r=0.98) when...
Mori R, Kodaka T, Sano T, Yamagishi N, Asari M, Naito Y.Laminar bone or primary plexiform tissue, not Haversian bone, shows an alternative concentric pattern of laminar-bone units or plates around the bone marrow periphery of long bones, although the laminar bone is gradually replaced by osteons during the growth period. One laminar-bone unit is constructed with a hypercalcified line in the center, woven bone on both sides of the line, and lamellar bone with laminated appositional lines. Such a laminar bone showing a homogeneous calcification has been reported in young calves and some young large animals, but it has not been reported in foals altho...
Tablin F, Walker NJ, Hogle SE, Pratt SM, Norris JW.To determine whether platelet growth factors are preserved in supernatants obtained from rehydrated trehalose-stabilized, freeze-dried (lyophilized) equine platelets and whether those growth factors stimulate fibroblast proliferation and migration and enhance fibroblast-associated contraction in a collagen gel assay. Methods: 6 clinically normal adult horses. Methods: Blood samples were obtained from 6 horses, and washed platelets were prepared via differential centrifugation. Washed platelets were freeze-dried in a physiologic buffer with a mixture of trehalose and polyethylene glycol 4000. R...
Allen WR, Wilsher S, Tiplady C, Butterfield RM.The growth parameters exhibited by seven Thoroughbred (Tb) foals that had experienced a 'restricted' in utero existence following transfer as embryos to the uteri of smaller Pony (P) mares (Tb-in-P) and, conversely, six P foals that experienced a 'luxurious' in utero existence after transfer to larger Tb mares (P-in-Tb), were compared from birth to 3 years of age with those exhibited by six normal Tb-in-Tb and six P-in-P foals conceived by within-breed artificial insemination. Bodyweight, height at the withers, girth, poll-to-nose length, crown-rump length and three foreleg longbone measuremen...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Silver K, Desormaux A, Freeman LC, Lillich JD.Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evidence indicates that the ulcerogenic properties of some NSAIDs are not exclusively the result of inhibition of cyclooxygenase isoforms in the GI tract, and other mechanisms, including inhibition of cell migration and epithelial restitution, are being explored. Recently, microarray analysis was used ...
Zayed M, Adair S, Dhar M.Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in ...
Hendesi H, Stewart S, Gibison ML, Guehring H, Richardson DW, Dodge GR.Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated a...
Bianchessi M, Chen Y, Durgam S, Pondenis H, Stewart M.Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with ...
Müller K, Ellenberger C, Schoon HA.Cyclical ovaries of 18 mares were examined histologically and immunohistochemically for vascular endothelial growth factor A and B (VEGF A; VEGF B), angiopoietin1 and 2 (Ang1; Ang2), vascular endothelial growth factor receptor 1 and 2 (VEGF-R1; VEGF-R2), angiopoietin receptor (Tie2) and von Willebrand factor. The most intensive coexpression of the examined factors and receptors was detected in the periovulatory period, when a distinctive ovarian angiogenesis takes place, being essential for tertiary follicle maturation and for the endocrine function of the Corpus luteum. Based on the immunohis...
Davidson TR, Chamberlain CS, Bridges TS, Spicer LJ.Little is known regarding the hormonal regulation of granulosa cell steroidogenesis and the ovarian insulin-like growth factor (IGF) system in the mare. The objectives of this study were to determine, first, if estradiol, insulin, and/or FSH affect steroid production by equine granulosa cells (experiment 1) and, second, if the components of the IGF system are produced by equine granulosa cells in culture as well as whether estradiol, insulin, and/or FSH affects IGF and/or IGF-binding protein (IGFBP) production by equine granulosa cells (experiment 2). Granulosa cells from small (6-15 mm), medi...
Hess S, Gulati R, Peluso JJ.The present studies showed that sequential treatment with equine CG (eCG) and hCG not only induced an increase in ovarian weight, but also caused an estimated 4.6-fold increase in the number of ovarian surface epithelial cells. In addition, eCG-hCG treatment increased ovarian hepatocyte growth factor (HGF) messenger RNA levels. These studies also demonstrated that rat primary ovarian surface epithelial cells as well as a cell line derived from rat ovarian surface epithelium (i.e. ROSE-179 cells) do not express the LH (hCG) receptor. Both of these cells express c-Met, the receptor for HGF. To a...
Beythien E, Aurich C, Wulf M, Aurich J.Seasonal changes in metabolic rate have been shown in horses and we hypothesized that this leads to the birth of smaller foals early in the year. Mares and their foals were assigned to three groups by day of foaling within the year (e.g. 1 January = day 1): Group 1 (n = 10) day 40-65, group 2 (n = 8) day 67-92, group 3 (n = 9) day 94-121. Groups did not differ with regard to parity. In foals, height at withers and body weight were determined on days 1-5 and weekly until 12 weeks of age. Chest circumference, distances fetlock to carpus, carpus to elbow, poll to nose and crown-rump lengt...
Ongchai S, Somnoo O, Kongdang P, Peansukmanee S, Tangyuenyong S.We investigated the effect of transforming growth factor beta 1 (TGF-β1) on equine hyaluronan synthase 2 () gene expression and hyaluronan (HA) synthesis in culture models of articular chondrocytes. Equine chondrocytes were treated with TGF-β1 at different concentrations and times in monolayer cultures. In three-dimensional cultures, chondrocyte-seeded gelatin scaffolds were cultured in chondrogenic media containing 10 ng/mL of TGF-β1. The amounts of HA in conditioned media and in scaffolds were determined by enzyme-linked immunosorbent assays. mRNA expression was analyzed by semi-quantita...
Reed SA, Johnson SE.Recovery from tendon injury is based on long periods of rest, which results in sub-optimal repair, often replacing tendon with fibrocartilage scar tissue. Recently, the use of stem cells in equine tendon repair has been attempted with variable success. The objective of this work was to determine the expression of scleraxis (scx) and tenascin C (TnC), two markers of tenocytes, in adipose (AdMSC) and umbilical cord blood (UCB) stem cells during culture on various substrata and in response to fibroblast growth factor (FGF) treatment. Equine UCB and AdMSC were cultured on gelatin-coated plasticwar...
Gabrielyan A, Knaak S, Gelinsky M, Arnhold S, Rösen-Wolff A.In vivo tissue regeneration depends on migration of stem cells into injured areas, their differentiation into specific cell types, and their interaction with other cells that are necessary to generate new tissue. Human mesenchymal stem cells, a subset of bone marrow stromal cells (BMSCs), can migrate and differentiate into osteoblasts in bone tissue. This can be facilitated by recombinant growth factors and cytokines. In many animal species, the availability of genomic sequences, recombinant proteins, and/or antibodies is limited so that new approaches are needed to generate resources that fac...
Cochrane CA.Abstract Wound models attempt to simulate the natural healing processes in wounds. However, all models have significant limitations due to the complexity of the tissue repair process. Much can be learned from wound models in vitro by the use of cell culture techniques. The horse can provide a suitable naturally occurring model of chronic wound healing because it has many similarities to wound healing encountered in human medicine. The tissue architecture was investigated with regard to extracellular matrix and growth factor distribution during wound healing and growth factors were consisten...