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.
Wormstrand BH, Fjordbakk CT, Griffiths DJ, Lykkjen S, Olstad K.Growth cartilage is found in the articular-epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies. Objective: To describe...
Chapman HS, Gale AL, Dodson ME, Linardi RL, Ortved KF.Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are being investigated for their potential in the treatment of musculoskeletal injuries, including tendon and ligament lesions, and cartilage lesions. Culture expansion of cells has traditionally been performed in medium supplemented with fetal bovine serum (FBS), however, concerns regarding the antigenicity and potential viral or prion contamination of FBS have prompted interest in alternative medium supplements. Platelet lysate (PL) contains elevated concentrations of growth factors, including transforming growth factor-β (TGF-β), pla...
Moshage SG, McCoy AM, Polk JD, Kersh ME.Bone adaptation is in part driven by mechanical loading, and exercise during youth has been shown to have life-long benefits for bone health. However, the development of early exercise-based interventions that reduce the incidence of fractures in racing horses is limited by the lack of characterization of normal development in growing bone. Previous efforts to quantify bone development in the horse have relied on repeated radiographs or peripheral quantitative computed tomography scans, which are limited in their assessment of the entire bone. In this study, we acquired computed tomography sca...
Garbin LC, Olver CS.Autologous platelet-rich plasma (PRP) is a biological preparation made from the patient's own plasma that contains a platelet concentration above the whole blood baseline. Owing to the release of growth factors and other cytokines after degranulation, platelets have a central role in inflammation and in different stages of the healing process. For this reason, PRP-derived products have been used to enhance healing of musculoskeletal injuries and modulate progression of inflammatory processes, including osteoarthritis (OA). Osteoarthritis is one of the main causes of musculoskeletal disabilitie...
Camargo Garbin L, McIlwraith CW, Frisbie DD.Platelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it's widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need fo...
Seidel SRT, Vendruscolo CP, Moreira JJ, Fülber J, Ottaiano TF, Oliva MLV, Michelacci YM, Baccarin RYA.Blood-derived autologous products are frequently used in both human and equine medicine to treat musculoskeletal disorders. These products, especially the platelet-rich plasma (PRP), may contain high concentrations of growth factors (GFs), and thus improve healing in several tissues. Nevertheless, the procedures for preparation of PRP are currently non-standardized. Several protocols, which are based on distinct centrifugation patterns (rotation speed and time), result in PRPs with different characteristics, concerning platelet and GFs concentrations, as well as platelet activation. The aim of...
McClain AK, McCarrel TM.Platelet-rich plasma (PRP) is a therapeutic biologic that is used for treatment of musculoskeletal pathologies in equine athletes. Due to the expense of PRP kits, and the volumes obtained, freezing aliquots for future dosing is common. Aliquots of PRP are also commonly frozen for later analysis of growth factor concentrations in in vitro research. A variety of freezing methods are used and storage duration until analysis is often not reported. The optimal frozen storage conditions and duration to maintain concentrations of commonly measured growth factors and enzymes in PRP are unknown. Our ob...
Jiménez-Aristazábal RF, Carmona JU, Prades M.The aims of the present study were (1) to describe the microscopic and ultrastructural appearance of equine platelet-rich fibrin (PRF) clots and (2) to determine the release and degradation of transforming growth factor beta 1 (TGF-β) and insulin-like growth factor type I (IGF-I) from PRF clots incubated over 14 days. Whole blood from six horses was collected into plain tubes and centrifuged at 240 g for 8 minutes. Clots were evaluated by histology and by both transmission and scanning electronic microscopy (TEM and SEM). Growth factor concentrations were measured by ELISA at 48-hour inter...
Ishak GM, Dutra GA, Gastal GDA, Elcombe ME, Gastal MO, Park SB, Feugang JM, Gastal EL.This study aimed to gain insight on the effect of different seasons of the year on the expression pattern of growth factor and hormone receptors involved in follicle development. A novel follicle wall biopsy technique was used to collect in vivo follicle wall layers (ie, granulosa, theca interna, and theca externa) and follicular fluid samples from growing dominant follicles, simultaneously and repeatedly, using the same mares during the spring anovulatory (SAN), spring ovulatory (SOV), summer (SU), and fall ovulatory (FOV) seasons. The immunofluorescent expression patterns of epidermal growt...
Fradinho MJ, Mateus L, Bernardes N, Bessa RJB, Caldeira RM, Ferreira-Dias G.Development of a healthy musculoskeletal system is of high concern for horse breeders and users. A longitudinal field study was performed in order to: (i) evaluate growth patterns and long-term changes on bone quality, bone metabolism, growth factors and metabolic variables in the Lusitano horse; and (ii) retrospectively assess whether these changes were related with radiographic findings regarding osteochondrosis-like lesions (OC) at the onset of training. Thirty-four Lusitano foals born and raised at four stud-farms, were periodically weighed (BW), and measured (withers height-WH) from birth...
Di Filippo PA, Dias Meireles MA, Ribeiro LMF, de Lannes ST, Meireles NFT, Viana IS, Hokamura HK.In this study, the effect of early exercise, age, body weight (BW), and growth on the articular cartilage and subchondral bones of the tarsocrural joints was evaluated in 40 young Mangalarga Marchador horses allowed free choice exercise in pasture. Twenty of the horses had additional controlled exercise 3 days per week from a mean age of 30 ± 20 days until 36 months. The training program consisted of an increasing number of 15-minute gallop sprints in an oval paddock with a concrete floor covered by a thick layer of sand. BW, withers height (WH), and neck circumference were measured and bo...
Smit Y, Marais HJ, Thompson PN, Mahne AT, Goddard A.Osteoarthritis is a common cause of lameness in horses, resulting in poor performance. Intra-articular platelet-rich plasma can deliver a collection of bioactive molecules, such as autologous growth factors and proteins involved in the quality of tissue repair. Horses (n=5) with osteoarthritis affecting antebrachiocarpal, middle carpal or metacarpophalangeal joints, and horses (n=5) without osteoarthritis of the corresponding joints (radiographically free of osteoarthritis), were used for the production of platelet-rich plasma which was subsequently injected into selected joints. Clinical and ...
van Eps AW, Burns TA.Laminitis is a consequence of primary disease processes elsewhere in the body. The key pathophysiologic events are insulin dysregulation in endocrinopathic laminitis, ischemia in supporting limb laminitis, and inflammation in sepsis-related laminitis. These apparently disparate mechanisms converge to cause lamellar attachment failure through epithelial cell adhesion loss and stretch, possibly mediated by common growth factor signaling pathways. Tissue damage through mechanical distraction, inflammation, pain, and a proliferative epithelial healing response are features of acute laminitis regar...
Polly SS, Nichols AEC, Donnini E, Inman DJ, Scott TJ, Apple SM, Werre SR, Dahlgren LA.Adipose-derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic-adherent adipose tissue-derived stromal cells (ASC) when culture-expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expressi...
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...
Hyttinen MM, Holopainen J, van Weeren PR, Firth EC, Helminen HJ, Brama PA.The aim of this study was to record growth-related changes in collagen network organization and proteoglycan distribution in intermittently peak-loaded and continuously lower-level-loaded articular cartilage. Cartilage from the proximal phalangeal bone of the equine metacarpophalangeal joint at birth, at 5, 11 and 18 months, and at 6-10 years of age was collected from two sites. Site 1, at the joint margin, is unloaded at slow gaits but is subjected to high-intensity loading during athletic activity; site 2 is a continuously but less intensively loaded site in the centre of the joint. The degr...
Becvarova I, Buechner-Maxwell V.The nutrition and nutritional status of the mare, as well as foal's nutrient intake from colostrum, milk and creep feed, are critical factors that are known to influence the growth period of the foal. Long-term effects of mare and foal nutrition are not well recognised or understood in the horse but may have the greatest impact on the animal's health and use when mature. Both under- and overfeeding can negatively influence important characteristics such as bone development and neurological function The risk of developing debilitating diseases such as metabolic syndrome may also be increased by...
Saito S, Sawai K, Minamihashi A, Ugai H, Murata T, Yokoyama KK.We describe here the isolation and maintenance of pluripotent embryonic stem (ES) cells from equine blastocysts that have been frozen and thawed. Equine ES cells appear to maintain a normal diploid karyotype in culture. These cells express markers that are characteristic of mouse ES cells, namely, alkaline phosphatase, stage-specific-embryonic antigen 1, STAT3, and Oct4. We also describe protocols for the induction of differentiation in vitro to neural precursor cells in the presence of basic fibroblast growth factor (bFGF), epidermal growth factor, and platelet-derived growth factor and to he...
Ortved KF, Nixon AJ, Mohammed HO, Fortier LA.To evaluate the long-term clinical outcome after allogeneic chondrocyte and insulin-like growth factor-I (IGF-I) grafting of subchondral cystic lesions (SCLs) of the femoral condyle in horses. Objective: To test the hypothesis that chondrocyte and IGF-I grafts will improve the long-term clinical outcome in arthroscopically debrided SCLs. Methods: Medical records of 49 horses with SCLs of the femoral condyle treated by debridement and implantation of chondrocytes and IGF-I were reviewed. Preoperative radiographs were obtained, and caudocranial radiographic projections were used to establish a r...
Murphy DJ, Nixon AJ.To examine the site-specific and dose-dependent effects of insulin-like growth factor I (IGF-I) on normal equine tendon in vitro. Methods: Superficial digital flexor tendon explants derived from a euthanatized 3-year-old horse. Methods: Explants in culture were treated with 0, 100, 250, or 500 ng of IGF-I/ml for 14 days with an end-stage radiolabel of 20 microCi of [3H]proline/ml or 5 microCi of [3H]thymidine/ml. The tendon tissues were then analyzed biochemically for hydroxyproline content by reverse-phase high-performance liquid chromatography, DNA content by fluorometry, and glycosaminoglyc...
Semevolos SA, Nixon AJ, Brower-Toland BD.To determine molecular changes in the expression of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in horses with osteochondrosis, and to characterize expression of matrix aggrecan and collagen types I, II, and X in articular cartilage of affected joints. Methods: Articular cartilage from affected stifle or shoulder joints of 11 horses with naturally acquired osteochondrosis and corresponding joints of 11 clinically normal horses. Methods: Harvested specimens were snap frozen in liquid nitrogen, and total RNA was isolated. Specimens were fixed in 4% paraf...
Fretz PB, Cymbaluk NF, Pharr JW.Long-bone growth at the distal ends of the radial bones, the distal ends of the 3rd metacarpal bones, the distal ends of the 3rd metatarsal bones, and the proximal ends of the proximal phalangeal bones (of thoracic and pelvic limbs) was quantitatively analyzed in 9 Thoroughbred-Quarter Horse foals from birth to 2 years of age. Metal growth markers were surgically implanted in the bones of the animals at 2 to 4 days of age. Radiographs of the bones were made on the day of surgical manipulation, the next day, and then once a week for 8 months, and once a month thereafter for an additional 18 mon...
van Weeren PR, Sloet van Oldruitenborgh-Ooste , Barneveld A.The influence of inherent variables (sex, birth weight, final achieved height, monthly weight gain rates and osteochondrosis (OC) status of the parents) on the occurrence of osteochondrotic lesions in the femoropatellar and tarsocrural joints in a group of foals was investigated as part of a research project aimed at the study of the development of osteochondrosis and the influence of exercise on the development of the musculoskeletal system in Warmbloods. The foals were genetically predisposed to develop OC, being offspring of sires that all had radiographically proven OC in either the femoro...
Allen WR, Gower S, Wilsher S.Polyclonal antisera for vascular endothelial growth factor (VEGF) and its two main receptor molecules, VEGF-I (Flt) and VEGF-II (KDR), were used in a conventional immunocytochemical staining method to localize these angiogenic ligand molecules in the endometrium and placenta of the mare during the oestrous cycle and pregnancy. The anti-VEGF and anti-Flt sera both labelled the lumenal and glandular epithelia of the endometrium throughout the oestrous cycle and both the invasive trophoblast cells of the endometrial cups and the non-invasive trophoblast of the allantochorion in pregnancy. The ant...
Holopainen JT, Brama PA, Halmesmäki E, Harjula T, Tuukkanen J, van Weeren PR, Helminen HJ, Hyttinen MM.The effects of growth and maturation on the mineral deposition and the collagen framework of equine subchondral bone (SCB) were studied. Methods: Osteochondral specimens (diameter 6 mm) from the left metacarpophalangeal joint of 5-(n=8), 11-(n=8) and 18-month-old (n=6) horses were investigated at two differently loaded sites (Site 1 (S1): intermittent peak loading; Site 2 (S2): habitual loading). The SCB mineral density (BMD) was measured with peripheral quantitative computer tomography (pQCT), and the data were adjusted against the volume fraction (Vv) of the bone extracellular matrix (ECM). ...
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...
Stewart AA, Byron CR, Pondenis HC, Stewart MC.To determine whether expansion of equine mesenchymal stem cells (MSCs) by use of fibroblast growth factor-2 (FGF-2) prior to supplementation with dexamethasone during the chondrogenic pellet culture phase would increase chondrocytic matrix markers without stimulating a hypertrophic chondrocytic phenotype. Methods: MSCs obtained from 5 young horses. Methods: First-passage equine monolayer MSCs were supplemented with medium containing FGF-2 (0 or 100 ng/mL). Confluent MSCs were transferred to pellet cultures and maintained in chondrogenic medium containing 0 or 10(7)M dexamethasone. Pellets were...
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...
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...
Zanotto GM, Liesbeny P, Barrett M, Zlotnick H, Frank E, Grodzinsky AJ, Frisbie DD.Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor-functionalized self-assembling KLD hydrogel ("functionalized hydrogel") has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Controlled laboratory study. Bilater...
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...
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...
Campos-Chillon F, Farmerie TA, Bouma GJ, Clay CM, Carnevale EM.We hypothesised that advanced mare age is associated with follicle and oocyte gene alterations. The aims of the study were to examine quantitative and temporal differences in mRNA for LH receptor (LHR), amphiregulin (AREG) and epiregulin (EREG) in granulosa cells, phosphodiesterase (PDE) 4D in cumulus cells and PDE3A, G-protein-coupled receptor 3 (GPR3), growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and mitochondrial (mt) DNA in oocytes. Samples were collected from dominant follicles of Young (3-12 years) and Old (≥20 years) mares at 0, 6, 9 and 12h after admi...
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...
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...
Haupt JL, Donnelly BP, Nixon AJ.To evaluate the effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on the metabolic function and morphologic features of equine superficial digital flexor tendon (SDFT) in explant culture. Animals-6 euthanized horses (2 to 5 years old). Methods: Forelimb SDFT explants were cultured for 6 days as untreated control specimens or treated with rhPDGF-BB (1, 10, 50, or 100 ng/mL of medium). Treatment effects on explant gene expression were evaluated via real-time PCR analysis of collagen type I, collagen type III, PDGF-A, and PDGF-B mRNA. Explants were assayed for total colla...
Haythorn A, Young M, Stanton J, Zhang J, Mueller POE, Halper J.Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGFβ) family, impacting synthesis of proteoglyca...
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...
Fortier LA, Nixon AJ, Mohammed HO, Lust G.To determine the effects of transforming growth factor-beta 1 (TGF-beta 1) on the synthesis of DNA, collagen, and proteoglycans (PG) by equine chondrocytes. Methods: Articular cartilage obtained from multiple joints of a 4-month-old foal. Methods: Chondrocytes were isolated by collagenase digestion, cultured in monolayer, trypsinized, and implanted at a cellular density of 10 x 10(6) chondrocytes/ml in a three-dimensional fibrin matrix. Chondrocytes in culture were supplemented with TGF-beta 1 at concentrations of 0, 1, 5, or 10 ng/ml in serum-free medium or medium containing fetal bovine seru...
