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.
Gunn HM.A modification of the histochemical reaction to demonstrate myosin adenosine triphosphatase activity in skeletal (striated) muscle was used to define the density of capillaries in transverse sections of 3 muscles (semitendinosus, diaphragm, and pectoralis transversus) of horses and dogs. Thoroughbred horses and Greyhound dogs, breeds noted for their speed in running, were compared with other members of their respective species. Thoroughbred cross horses were grouped with non-Thoroughbreds for comparison with Thoroughbreds. The area of muscle supplied by a capillary was remarkably similar in mu...
Goyal HO, MacCallum FJ, Brown MP, Delack JB.Measurements were made of growth at the extremities of all the long bones of the left limbs of 23 horses between 52 and 104 days of age. Growth rates were more rapid in the younger than in the older animals. Growth was more rapid in the hind limb than in the forelimb. Growth rates were greater for males than in females. Although this age group represents only two of the 60 or so months necessary for maturity to be reached, oxytetracycline bone-labelling produced results which are more precise than measurements obtained by other methods. This study provides a substantial amount of data for an a...
Stromberg B.There appears to be an increasing incidence of osteochondrosis in young fast-growing horses in Europe and the USA. The disease is thought to be congenital in type and affects endochondral ossification in growing bones. It can be localised to one joint or may be a generalised condition. The clinical manifestations of the disease lead to a secondary chronic degenerative joint disease in adult animals. There is a genetic predisposition to the condition which is associated with rapid growth and excessive high energy feeding. The careful genetic selection of bloodstock and restricted intake in earl...
Washburn LR, Somerson NL.Crude lipoprotein-containing fractions obtained from sera of three different animal species were tested, in combination with bovine serum in Mycoplasma pneumoniae culture medium. All sera yielded at least one lipoprotein-containing component which was considerably more effective in promoting mycoplasma growth than the unfractionated serum sample from which it was derived. The very low activity of certain whole-serum samples tested in this investigation suggests that toxic substances may be present in whole serum which are not contained in the lipoprotein preparations. The greatest activity app...
Gunn HM.The numbers of fibres in the complete cross section of the semitendinosus were estimated in 58 equines and 59 canines of differing types. Animals selected for swiftness--thoroughbred horses and greyhounds--have a greater number of fibres in a cross section of their semitendinosus than other members of their species, whether as neonates or as adults. The numbers of fibres in the cross section increases during growth in both types of animal in each species.
Gunn HM.The mean fibre areas of samples from m. semitendinosus, m. diaphragma and m. pectoralis transversus of thoroughbred horses and greyhounds have been compared with those in similar samples from other members of their species. Athletes (greyhounds and thoroughbreds) have larger fibres in the semitendinosus and diaphragm than their fellows. However, the mean area of pectoralis transversus is similar in the two types of animal within each species. During growth the mean fibre areas increase to a greater extent in athletes than in non-athletes. Detraining adult greyhounds for a period of one year di...
Wilson RT.Equines have been largely ignored in modern scientific literature on domestic animals, probably because they are not providers of meat and milk. Their contribution to the economy in the Sudan, however, is considerable and they are the principal means of transport both as baggage and as riding animals. They also play an important role in the supply of fuel and the distribution of domestic water in the larger villages and towns. Information on population structure is provided and descriptions, with particular reference to withers height and weight, are given of two types of donkey and of the hor...
Pine L, Reeves MW.Various sugars were tested for their effect on the differential rate of synthesis of M protein during the growth of Streptococcus pyogenes strain 0055 M12T12. In a semisynthetic medium alone, a high rate of M protein synthesis occurred with glucose as a substrate; decreasing rates of synthesis occurred with sucrose and trehalose, in that order, although the rates of growth were approximately equal with all sugars. A period of derepressed synthesis of M protein occurred in the lag phase of growth and in the stationary period as the substrates were being depleted. Although glucose inhibited the ...
Campbell JR.Limb angulation in foals may be due to defects in epiphyseal growth plates. The present state of knowledge concerning rate of growth in foals and differences in growth of different epiphyseal plates is reviewed and the importance of accurate knowledge of these parameters in treatment of angulation by unilateral retardation of an epiphyseal growth plate is stressed. Retardation of epiphyseal plate growth by compression wiring is described and its advantages in comparison with staplings are suggested. Compression wiring was used in 3 cases in which age, bone width and the degree of angulation we...
Butler KD, Hintz HF.A pelleted ration was fed limited or ad libitum to two groups of seven Shetland 8-month-old ponies for 117 days. During the last 56 days, gelatin was added to the diets of four animals in each of the two intake groups. Gelatin was added at levels of 30 and 90 g per 100 kg body weight for the first and second 28-day periods, respectively.
Ponies fed the diet ad libitum consumed 180% more feed, had 50% greater rate of hoof growth (.384 ± .009 vs .254 ± .008 mm/d), 200% greater increase in height at the withers and 425% greater increase in body weight than ponies fed the limited level. The h...
Green DA.One hundred and four animals aged 13-18 months were measured at monthly or two monthly intervals, as were comparable numbers of animals 19-36 months old. Height, girth and circumference of the cannon bone below the knee were recorded, measurements for colts and fillies are shown separately. The average height at 18 months was 148 cm (15.01/2 h.h.) and at 36 months 156 cm (15.31/2 h.h.).
Irvine CH, Evans MJ.Total tyhroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and free triiodothyronine (FT3) concentrations in foal umbilical cord blood were respectively 14, 5 7 and 3 times the concentrations of these hormones in adult horse blood. The TT4 levels in foals declined rapidly to reach adult concentrations by Day 16 and FT4 levels declined steadily during the first 3 months of life. Foal TT3 levels rose during the first 10 hr after birth and thereafter declined, although they were still X2-5 higher than adult levels at 3 months of age. Levels of FT3 similarly increased after birth be...
Lowe JE, Baldwin BH, Foote RH, Hillman RB, Kallfelz FA.Surgical thyroidectomies (Thx) were per-formed in 6 yearling grade horse colts, (3 males, 3 females). Five control colts (3 males, 2 females) were included and comparative studies were carried out for 67 weeks. The comparative measurements included rectal temperature, heart rate, feed consumption, packed cell volume, serum cholesterol, serum calcium, serum phosphorus, serum TO height, heart girth, body weight, epiphyseal plate closure and tooth eruption times. A thyroprotein supplement was fed to the Thx males during weeks 46 to 53. The Thx animals failed to grow in height, were sensi-tive to ...
Thway TM, Wolfe MW.Equids and primates are the only species known to express the placental hormone chorionic gonadotropin (CG). CG is a member of the heterodimeric glycoprotein family and is composed of an alpha subunit linked to a hormone-specific beta subunit. Previously, we have reported that epidermal growth factor (EGF) regulates the equine glycoprotein hormone alpha subunit promoter through a protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signal transduction pathway in trophoblasts. The current study investigates the regulatory element/factors involved in the induction of equine glycoprotei...
Hortensius RA, Harley BA.The design of biomaterials for regenerative medicine can require biomolecular cues such as growth factors to induce a desired cell activity. Signal molecules are often incorporated into the biomaterial in either freely-diffusible or covalently-bound forms. However, biomolecular environments in vivo are often complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides found in the extracellular matrix, are involved in transient sequestration of growth factors via charge interactions. Biomaterials mimicking this phenomenon may offer the potential to amplify local biomolecular...
Carter CA, Jolly DG, Worden CE, Hendren DG, Kane CJ.Nonhealing wounds of the lower equine limb represent a challenging model. The platelet is a natural source of a myriad of growth factors and cytokines that promote wound healing. This study evaluates the potential of platelet derived factors to enhance wound healing in the lower equine limb. Platelets were isolated from horse blood and activated with thrombin, a process known to induce growth factor release. This produced a platelet gel composed of platelet-rich plasma (PRP). To test this all-natural wound healant, 2.5-cm(2) full thickness cutaneous wounds were created below the knee and hock ...
Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA.Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Ten...
Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK.Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2. RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs). A co-culture system was utilized t...
Watson ED, Zanecosky HG.Immunosuppressive substances which interfere with lymphocyte blastogenesis are released in vitro by embryos and endometrium from mares in early pregnancy. Immunosuppression was not evident when tissues were cultured in the presence of indomethacin (a prostaglandin-synthesis inhibitor). Various prostaglandins (PGs) were added to equine lymphocytes and lymphocyte proliferation was measured after the addition of concanavalin A (Con A) or phytohaemagglutinin A (PHA). PGE2 and PGF2 alpha inhibited Con A-induced blastogenesis down to final concentrations of 1.8 x 10(-9) M and 1.3 x 10(-6) M, respect...
Silver IA, Eisinger M.We have examined the possible regulatory role of epidermal cell extract(s) (ECE) on skin cells, namely fibroblasts and keratinocytes, both in vivo and in vitro with particular reference to modification of scar formation. In an experimental wound model in pigs, it was found that extracts of cultured human and pig keratinocytes stimulated replication of epidermal cells and their migration from wound edges and remnants of hair follicles and sebaceous glands, together with hair growth, but at the same time suppressed fibroblast proliferation in the dermis. Sections of healing skin wounds that had ...
Barshick MR, Gonzalez ML, Busse NI, Helsel PJ, Johnson SE.Satellite cell (SC) activation is defined as the time frame during which the stem cell becomes poised to reenter G1 of the cell cycle. The growth factors and events leading to full mitotic activation in equine SCs remain largely unknown. Insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), and fibroblast growth factor 2 (FGF2) are sequentially transcribed during the muscle repair and recovery period following strenuous exercise in adult horses. Expression of IGF-I occurs within 24 h of the postexercise recovery period suggesting it may affect early SC actions. As a first step,...
Giraldo CE, Álvarez ME, Carmona JU.To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Methods: Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Results: Growth factor concentrations were signific...
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 ...
Buffington CA, Knight DA, Kohn CW, Madigan JE, Scaman PA.The effects of 2 liquid formula diets differing in protein source were evaluated in orphan foals. The response of 7 foals fed a diet containing casein as the protein source, and 6 foals fed a diet containing a combination of whey and casein, was compared with the response in a reference group of 8 mare-raised foals. Orphaned foals were fed 150 kcal/kg of body weight/d, divided into 6 equal feedings of 25 kcal/kg. Formula intake was comparable among the experimental groups, and foals fed the liquid formula diet grew as well as mare-raised foals. There was no difference among groups in mean dail...
Lorenzo PL, Liu IK, Illera JC, Picazo RA, Carneiro GF, Illera MJ, Conley AJ, Enders AC, Illera M.Epidermal growth factor (EGF) has been reported to promote different functions in mammalian ovaries, including oocyte maturation. The aim of the present study was to establish: that EGF influences oocyte maturation in ovine and equine, that a tyrosine kinase-dependent intracellular mechanism mediates EGF effect and, that EGF-R receptor is detectable in ovarian follicles by immunohistochemistry methods. Selected ovine and equine oocytes were aspirated from 2-5 mm (ovine) or 25 mm (equine) follicles and cultured in TCM 199 for 22 (ovine) or 36 hours (equine). They are then subjected to culture w...
Johannessen MK, Skretting G, Ytrehus B, Røed KH.Endochondral bone formation is an important process in development and growth of the skeleton; still many of the mechanisms of growth cartilage remain unknown. The aim of this study was to identify genes specifically expressed in growth cartilage by constructing a subtraction cDNA library of the articular-epiphyseal cartilage complex from neonatal foal. Two hundred and eighty-four differently expressed clones, representing five novel and 37 known genes, were detected by subtraction hybridization. The tissue specificity of these genes was verified by reverse Northern analysis, and tissue distri...
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...
Lackey BR, Gray SL, Henricks DM.The multi-functional proteins, insulin-like growth factor-I (IGF-I) and leptin were present in seminal plasma from different species. Concentrations of IGF-I in equine and porcine semen were 20 and 17.5 ng/ml, respectively. Seminal plasma concentrations of leptin were 1 ng/ml in human and 11 ng/ml in porcine samples.
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...
Clutterbuck AL, Harris P, Allaway D, Mobasheri A.The extracellular matrix (ECM) of connective tissue is constantly being remodelled to allow for growth and regeneration. Normal tissue maintenance requires the ECM components to be degraded and re-synthesised in relatively equal proportions. This degradation is facilitated by matrix metalloproteinases (MMPs) and their proteolytic action is controlled primarily by the tissue inhibitors of metalloproteinases (TIMPs). Both MMPs and TIMPs exist in a state of dynamic equilibrium, with a slight excess of one or the other depending on the need for either ECM breakdown or synthesis. Long-term disrupti...
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...
Mack JK, Remler HP, Senckenberg E, Kienzle E.The objective of this study was to investigate the effects of a different energy supply on the development of Warmblood foals with a focus on examining the recommended allowances of the German Society for Nutrition Physiology. Methods: Two groups of foals received different amounts of concentrates from the 1st until the 6th month of life. With regards to the total energy content, the rations were composed to either comply with the recommendations (6) (group "Norm", n=15) or to exceed those by approximately 20% (group "Zulage", n=16). The supply with concentrates of the group "Norm" aimed for a...
Lygren T, Hansen S, Langberg H, Fjeldborg J, Jacobsen S, Nielsen MO, Schjerling P, Markussen B, Thomsen PD, Berg LC.Insulin-like growth factor 1 (IGF-1) has important roles in anabolic processes in the musculoskeletal system and has been reported to decrease with age in both people and horses. Objective: The objective of this study was to determine serum IGF-1 levels in the aging horse from early to late adulthood (age range 5-27 years). Methods: Healthy horses (n = 72) were used in a cross-sectional study, while 37 paired serum samples were available for a longitudinal study. Serum IGF-1 protein was determined using an ELISA kit validated for use in equine samples. Results: No association was found betw...
Ríos DL, López C, Álvarez ME, Samudio IJ, Carmona JU.Platelet-rich plasma (PRP) preparations are a common treatment in osteoarthritis (OA) and inflammatory synovitis. However, there is ambiguity regarding the ideal concentration of leukocytes and platelets in these preparations necessary to induce an adequate anti-inflammatory and anabolic response in joint tissues, such as the synovial membrane. This research aimed to study, in normal synovial membrane explants (SME) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the pr...
Gomiero C, Bertolutti G, Martinello T, Van Bruaene N, Broeckx SY, Patruno M, Spaas JH.Tendons regenerate poorly due to a dense extracellular matrix and low cellularity. Cellular therapies aim to improve tendon repair using mesenchymal stem cells and tenocytes; however, a current limitation is the low proliferative potential of tenocytes in cases of severe trauma. The purpose of this study was to develop a method useful in veterinary medicine to improve the differentiation of Peripheral Blood equine mesenchymal stem cells (PB-MSCs) into tenocytes. PB-MSCs were used to study the effects of the addition of some growth factors (GFs) as TGFβ3 (transforming growth factor), EGF2 (Epi...
Schryver HF, Meakim DW, Lowe JE, Williams J, Soderholm LV, Hintz HF.The effect of level of protein intake on growth and calcium metabolism was studied in 24 foals. Starting at four months old, the foals were fed one of three diets containing all nutrients, with the exception of protein, at levels recommended by the United States National Research Council Subcommittee on Horse Nutrition for a 12 month period. The protein levels in the three diets were 9 per cent (low protein) 14 per cent (NRC recommended level) and 20 per cent (high protein). The foals fed the low protein diet were changed to the high protein diet after 140 days when they were nine months old. ...
Robert C, Valette JP, Denoix JM.There is limited published data on conformational changes in the forelimbs of growing foals. This study was designed to describe the changes in conformation of the carpus and distal forelimb from birth to weaning in foals of three different breeds. Evaluation of the conformation of the carpus, fetlock, pastern and foot was carried out in 134 Thoroughbreds, 162 French Trotters and 98 Selle Français (French Warmblood) within 1 month of age and then at approximately 2 month intervals until weaning at approximately 6 months of age. The prevalence of limb deviations decreased from birth to weaning...
Brown KA, Gregorio EN, Barot D, Usimaki A, Linardi RL, Missanelli JR, You Y, Robinson MA, Ortved KF.To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). Methods: 6 adult university-owned horses. Methods: For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was rep...
Quam VG, Belacic ZA, Long S, Rice HC, Dhar MS, Durgam S.Safe, efficacious therapy for treating degenerate deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) in navicular horses is critically necessary. While archetypal orthobiologic therapies for navicular disease are used empirically, their safety and efficacy are unknown. Mesenchymal stem cell-derived extracellular vesicles (EV) may overcome several limitations of current orthobiologic therapies. Objective: To (1) characterise cytokine and growth factor profiles of equine bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (BM-EV) and (2) evaluate the ...
