Topic:Growth Factors
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.
Immunohistochemical study of angiogenesis and angiogenic factors in equine granulosa cell tumours. The first part of our study (Müller et al., 2009) characterized angiogenesis in the equine cycling ovary through histomorphological and immunohistochemical examinations (vascular endothelial growth factors A and B [VEGF A, VEGF B], vascular endothelial growth factor receptors 1 and 2 [VEGF-R1, VEGF-R2], vascular angiopoietins 1 and 2 [Ang1, Ang2], angiopoietin receptor [Tie2], and von Willebrand Factor). Since angiogenesis plays an important role in development and growth of numerous tumours, the second part of our study involved a similar examination of 70 equine granulosa cell tumours (GCTt...
Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses. Tissue repair in musculoskeletal injuries is often a slow and sometimes incomplete process. Regenerative medicine based on the use of growth factors (GFs) and cell therapy is aimed at improving the quality and speed of tendon and ligament healing. The aim of this study was to evaluate the potential for the administration of a combination of autologous platelet-rich plasma (PRP) and freshly isolated bone marrow mononucleated cells (BMMNCs) in 13 competition horses affected by overuse musculoskeletal injuries (suspensory ligament desmopathy and superficial flexor tendinopathy) and refractory to ...
Influence of dietary methionine concentration on growth and nitrogen balance in weanling Quarter Horses. Twenty-four Quarter Horse weanlings (120 ± 10 d) were blocked by age into 4 groups (n=6) for a 56-d trial to evaluate the influence of dietary Met concentration on growth and N balance. Weanling horses were housed by block and individually fed concentrates twice daily at 1.75% BW (as-fed basis). Weanling horses were randomly assigned to 1 of 4 concentrate treatments: basal (0.20 Met), basal + 0.03% Met (0.23 Met), basal + 0.07% Met (0.27 Met), and basal + 0.11% Met (0.31 Met). Diets were formulated to be isonitrogenous and isocaloric and contained equal amounts of Lys and Thr. Coastal bermuda...
Effects of preparation method, shear force, and exposure to collagen on release of growth factors from equine platelet-rich plasma. To test the hypotheses that preparation method, exposure to shear force, and exposure to collagen affect the release of growth factors from equine platelet-rich plasma (PRP). Methods: PRP obtained from 6 horses. Methods: PRP was prepared via 2 preparation methods (tube and automated) and subjected to 6 treatment conditions (resting, detergent, exposure to shear via 21- and 25-gauge needles, and exposure to collagen [10 and 20 μg/mL]). Concentrations of platelet-derived growth factor, isoform BB (PDGF-BB); transforming growth factor β, isoform 1 (TGFβ₁); and insulin-like growth factor, iso...
Infrared spectroscopy reveals both qualitative and quantitative differences in equine subchondral bone during maturation. The collagen phase in bone is known to undergo major changes during growth and maturation. The objective of this study is to clarify whether Fourier transform infrared (FTIR) microspectroscopy, coupled with cluster analysis, can detect quantitative and qualitative changes in the collagen matrix of subchondral bone in horses during maturation and growth. Equine subchondral bone samples (n = 29) from the proximal joint surface of the first phalanx are prepared from two sites subjected to different loading conditions. Three age groups are studied: newborn (0 days old), immature (5 to 11 months ol...
Expansion of mesenchymal stem cells on fibrinogen-rich protein surfaces derived from blood plasma. Mesenchymal stem cells (MSCs) are present in low density in bone marrow and culture expansion is necessary to obtain sufficient numbers for many proposed therapies. Researchers have characterized MSC growth on tissue culture plastic (TCP), although few studies have explored proliferation on other growth substrates. Using adult equine MSCs, we evaluated proliferation on fibrinogen-rich precipitate (FRP) surfaces created from blood plasma. When seeded at 1 × 10(4) cells/cm(2) and passaged five times over 10 days, MSCs on FRP in medium containing fibroblast growth factor 2 (FGF2) resulted in a ...
Chromosomal assignment of R-spondin genes in the donkey (Equus asinus, 2n = 62). R-spondins constitute a recently discovered small family of growth factors, and the evidence of their role in several developmental pathways is growing fast. In this work we describe the chromosomal location of the four RSPO genes in the donkey. Using horse BACs, we localized RSPO1 on EAS 5q23, RSPO2 on EAS 12q13, RSPO3 on EAS 24q26, and RSPO4 on EAS 15p13. Moreover, RSPO2, RSPO3, and RSPO4 are the first genes mapped on donkey chromosomes 12, 24, and 15, respectively.
The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions. The repair process of tendon injuries, which are common in both human and equine athletes, is slow and the quality of the repair tissue is often inferior to the original tendon tissue, which frequently leads to re-injury. The relatively poor vascularization of tendons is considered to be one of the reasons for their limited healing potential. Recently, platelet-rich plasma (PRP), an autologous concentrate of platelets, rich in growth factors, has been shown to enhance the repair process of injured tendons. This effect has been ascribed to the high levels of growth factors in PRP, several of wh...
Platelet-derived growth factor acts via both the Rho-kinase and p38 signaling enzymes to stimulate contraction in an in vitro model of equine wound healing. Horses are more prone to complications in the wound healing process than other species, and problems such as chronic inflammation, delayed epithelialization, poor wound contraction, and exuberant granulation tissue are commonly seen, particularly in wounds on the distal limbs. In comparison, wounds of the oral mucosa heal rapidly in a scarless fashion with a high degree of wound contraction. The effect of platelet-derived growth factor BB (PDGF), insulin-like growth factor (IGF)-1, and transforming growth factor beta1 (TGFbeta1) on the contraction of a fibroblast-populated collagen matrix (FPC...
The use of amniotic membrane transplantation for ocular surface reconstruction: a review and series of 58 equine clinical cases (2002-2008). Amniotic membrane transplantation (AMT) is an effective clinical therapy for reconstruction of the ocular surface in human and veterinary patients. Amnion is avascular and strong, contains antiangiogenic and antiinflammatory properties and growth factors, and has properties that prevent or decrease fibrosis in healing tissue. Indications for its use are steadily growing and include grafting to replace diseased, missing or excised tissue, patching to support diseased tissue during the healing process and as a substrate for the expansion of epithelial cells for transplantation to the cornea. AMT...
Influence of intensity and changes of physical activity on bone mineral density of immature equine subchondral bone. Subchondral bone provides structural support to overlying articular cartilage and plays an important biomechanical role in osteochondral diseases. Mechanical features of bone correlate strongly with bone mineral density, which is directed by the loading conditions to which the tissue is subjected. Objective: To investigate the influence of physical activity levels on subchondral bone mineral density (sBMD) in foals during early development. Methods: Three groups of foals were subjected to different physical activity levels from birth until age 5 months. A proportion of these foals were subject...
Functional relationships among intrafollicular insulin-like growth factor 1, circulatory gonadotropins, and development of the dominant follicle in mares. The functional relationships among intrafollicular free insulin-like growth factor 1 (IGF1), circulatory gonadotropins, and development of the dominant follicle were studied in 40 mares in two experiments. A GnRH antagonist (Acyline) was given i.m. at the expected beginning of follicular deviation (largest follicle or F1> or =20mm; Day 0) alone (Acyline group) or in combination with intrafollicular treatment of F1 with rhIGF1 (Acyline/IGF1 group). In Experiment 1, blood samples, follicular-fluid samples, and diameter of F1 were taken on Days 1 and 2. In Experiment 2, daily follicular diamet...
Dermal fibroblast-mediated BMP2 therapy to accelerate bone healing in an equine osteotomy model. This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein-2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb-BMP2-treated ...
Changes in collagen fibril network organization and proteoglycan distribution in equine articular cartilage during maturation and growth. 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...
Isolation, growth and differentiation of equine mesenchymal stem cells: effect of donor, source, amount of tissue and supplementation with basic fibroblast growth factor. Mesenchymal stem cells (MSC) are increasingly used as therapeutical aid for the orthopaedic injuries in the horse. MSC populate different tissues but the most commonly used for clinical purposes are isolated from bone marrow or adipose tissue. The first objective of this study was to investigate if the donor animal, the tissue of origin and the technique of isolation could influence the number of MSC available for transplantation after a short-term expansion. The second aim was to devise a culture system capable of increasing MSC lifespan and we tested the effect of basic fibroblast growth fac...
Cholinergic stimulation attenuates the IL-4 induced expression of E-selectin and vascular endothelial growth factor by equine pulmonary artery endothelial cells. The endothelium plays a critical role in regulating leukocyte recruitment and migration during inflammation. Recent studies provide evidence that acetylcholine (ACh) and other cholinergic mediators block endothelial cells activation and leukocyte recruitment during inflammation. We thus postulated that the non-neuronal cholinergic system might modulate the recruitment of neutrophils during allergic pulmonary inflammation. In the present study, we examined the effects of cholinergic stimulation on the expression of neutrophil chemokines and adhesion molecules by endothelial cells stimulated by ...
Histomorphological and immunohistochemical study of angiogenesis and angiogenic factors in the ovary of the mare. 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...
Effects of extracorporeal shock wave therapy on wounds of the distal portion of the limbs in horses. To evaluate the effects of focused, extracorporeal shock wave therapy (ESWT) on the healing of wounds of the distal portion of the limbs in horses. Methods: Randomized controlled trial. Methods: 6 healthy adult horses. Methods: In each horse, a 4-cm-diameter full-thickness wound that included underlying periosteum was created on the dorsomedial aspect of each metacarpus and two 3-cm-diameter full-thickness wounds that included underlying periosteum were created on the dorsomedial aspect of each metatarsus. One randomly selected metacarpal wound and a randomly selected pair of metatarsal wounds...
Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons. Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with ...
Variations of plasmatic concentrations of Insulin-like Growth Factor-I in post-pubescent horses affected with developmental osteochondral lesions. Developmental osteochondral lesions are often encountered in the equine population and are a major cause of lameness. Different growth factors that act systemically as well as locally regulate the growth of cartilage. Among them is Insulin-like Growth Factor I that has been demonstrated to promote chondrocyte growth and differentiation and that has been shown to influence cartilage repair. The aims of this study were to investigate differences in circulating plasma levels of Insulin-like Growth Factor-I in post-pubescent horses affected with developmental osteochondral lesions compared to unaf...
Effects of platelet-rich plasma on the repair of wounds on the distal aspect of the forelimb in horses. To evaluate the effect of platelet-rich plasma on wounds on the distal aspect of the forelimb in horses. Methods: 6 mixed-breed 10- to 15-year-old mares. Methods: 3 wounds were created on metacarpal regions in each of 6 horses (n = 36 wounds total). Eighteen wounds were treated with platelet-rich plasma and bandaged, whereas 18 control wounds were similarly bandaged with no prior topical treatment. Decrease in wound surface area and the required number of excisions of exuberant granulation tissue were recorded until complete healing. Tissue specimens were taken from wounds at 1 week for histol...
Comparison of chondrogenic potential in equine mesenchymal stromal cells derived from adipose tissue and bone marrow. To compare the chondrogenic potential of adult equine mesenchymal stem cells derived from bone marrow (MSCs) or adipose tissue (ASCs). Methods: In vitro experimental study. Methods: Adult Thoroughbred horses (n=11). Methods: BM (5 horses; mean [+/-SD] age, 4+/-1.4 years) or adipose tissue (6 horses; mean age, 3.5+/-1.1 years) samples were obtained. Cryopreserved MSCs and ASCs were used for pellet cultures in stromal medium (C) or induced into chondrogenesis+/-transforming growth factor-3 (TGFbeta(3)) and bone morphogenic factor-6 (BMP-6). Pellets harvested after 3, 7, 14, and 21 days were exam...
In vivo effects of intra-articular injection of gelatin hydrogen microspheres containing basic fibroblast growth factor on experimentally induced defects in third metacarpal bones of horses. To evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing basic fibroblast growth factor (bFGF) on experimentally induced defects in third metacarpal bones (MC3s) of horses, in vivo. Methods: 6 healthy adult Thoroughbreds. Methods: Horses were anesthetized, and a hole (diameter, 4.5 mm) was drilled into the medial condyle of both MC3s of each horse. One milliliter (100 microg) of a solution of gelatin hydrogel microspheres (2 mg) containing bFGF was injected into the joint capsule of the right metacarpophalangeal joint of each horse (bFGF joint). One milli...
Matrix metalloproteinases in inflammatory pathologies of the horse. 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...
Assessment of platelet growth factors in supernatants from rehydrated freeze-dried equine platelets and their effects on fibroblasts in vitro. 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...
Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid. Equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. The present study further characterizes aspects of the association with BPV in 15 equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins E5 and E7, but these oncoproteins were not expressed by...
Changes in subchondral bone mineral density and collagen matrix organization in growing horses. 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). ...
Effect of dexamethasone supplementation on chondrogenesis of equine mesenchymal stem cells. 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...
Use of linear and non-linear functions to describe the growth of young sport- and race-horses born in Normandy. The objectives of this study were to establish standards for growth and to model the evolution of wither height (WH) between birth and adult age in different breeds of sport- and race-horses. Therefore, 398 foals, then yearlings of three different breeds, were measured regularly between birth and 18 months of age. Linear and non-linear functions were compared for describing the growth in each breed group. The monomolecular, Gompertz, logistic and cubic models correctly estimated WH in the three breeds during the first 2 years (R2 = 0.99, s.e. 3.9 to 4.5) and better than the cubic and quadratic...
Regenerative medicine for tendinous and ligamentous injuries of sport horses. After tendon injury, the scar tissue that replaces the damaged tendon results in a substantial risk for reinjury. The goal of regenerative therapies is to restore normal structural architecture and biomechanical function to an injured tissue. Successful restoration processes for any tissue are thought to recapitulate those of development, in which there are spatial and temporal interactions between scaffold, growth factors, and cell populations.