Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses

Dart, Andrew; Little, C.; Hughes, Clare Elizabeth; Chu, Qili; Dowling, B A; Hodgson, David; Rose, R. J.; Johnson, Kenneth A.

doi:10.2746/042516403776148165

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…Studies in animal models have shown that direct injection of IGF-I into the joint or administration of GH which results in an increase in the concentration of IGF-I in joint fluid are trophic for growth plate cartilage during normal development and for articular cartilage during the development of osteoarthritis (13, 39–42). IGF-I synergizes with other growth factors such as EGF, TGFα and FGF to enhanced proteoglycan synthesis and cartilage repair.…”

Section: Discussionmentioning

confidence: 99%

Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid

Busby

Yocum

Rowland

et al. 2009

Osteoarthritis and Cartilage

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Insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) are trophic factors for cartilage and have been shown to be chondroprotective in animal models of osteoarthritis. IGFBP-5 is degraded in joint fluid and inhibition of IGFBP-5 degradation has been shown to enhance the trophic effects of IGF-I. Objective To determine the identity of IGFBP-5 protease activity in human osteoarthritic (OA) joint fluid. Method OA joint fluid was purified and the purified material analyzed by IGFBP-5 zymography. Results Both crude joint fluid and purified material contained a single band of proteolytic activity that cleaved IGFBP-5. Immunoblotting of joint fluid for complement 1s (C1s) showed a band that had the same Mr estimate, e.g. 88 kDa. In gel tryptic digestion and subsequent peptide analysis by LC-MS/MS showed that the band contained human complement 1s. A panel of protease inhibitors was tested for their ability to inhibit IGFBP-5 cleavage by the purified protease. Three serine protease inhibitors, FUT175 and CP 143217 and CB-349547 had IC50’s between 1and 6 uM. Two other serine protease inhibitors had intermediate activity (e.g. IC50’s 20–40 uM) and MMP inhibitors had no detectible activity at concentrations up to 300 uM. Conclusion Human OA fluid contains a serine protease that cleaves IGFBP-5. Zymography, immunoblotting and LCMS/MS analysis indicate that complement 1s is the protease that accounts for this activity.

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Section: Discussionmentioning

confidence: 99%

Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid

Busby

Yocum

Rowland

et al. 2009

Osteoarthritis and Cartilage

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“…The most natural, effective and cost-efficient method to increase serum levels of IGF-I is through systemic administration of GH (Rosen 2000). Of noted interest to equine clinicians are studies which demonstrate the capacity of GH administration to reverse age-associated loss of bone marrow cells, improve recovery of skeletal muscle from hindlimb cast-immobilisation and to improve the healing capacity of cartilage (Dart et al 2003) and tendon (Rosen 2000). All of these beneficial effects of GH therapy may aid in the rehabilitation of individuals suffering musculoskeletal trauma as well as improve the quality of life for aged horses.…”

Section: Introductionmentioning

confidence: 99%

Age‐related changes in serum insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐3 and articular cartilage structure in Thoroughbred horses

Fortier

Kornatowski

Mohammed

et al. 2005

Equine Veterinary Journal

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Summary Reasons for performing study: Structural changes in articular cartilage associated with the ageing process require definition for investigators performing developmental and age‐related studies, for which information is lacking. Objectives: To 1) determine the onset and end of puberty as defined by serum insulin like growth factor (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3) concentrations and 2) correlate articular‐epiphyseal cartilage complex structural changes with the onset and end of puberty. Methods: IGF‐1 and IGFBP‐3 were measured in serum samples from normal female and male horses age 9‐715 days to determine peak and steady‐state values for horses transitioning through puberty. Osteochondral tissue sections were obtained from horses age 120‐840 days (4‐28 months) and examined histologically for cartilage canals and tidemark formation. Results: In male and female horses, serum IGF‐1/IGFBP‐3 concentrations peaked at approximately 225 days, defining the onset of puberty. Cartilage canals were absent from articular cartilage just prior to this time point. IGF‐1/IGFBP‐3 concentrations declined to steady‐state levels at approximately age 450 days, signalling exit from puberty and therefore the beginning of ageing. This time point correlated to initial formation of a tidemark in the osteochondral tissue sections. Conclusions: Horses may be considered pubescent at age 225‐450 days, and post pubescent and ageing after age 450 days. Potential relevance: Defining the normal post natal to post pubescent concentrations for serum IGF‐I and serum IGFBP‐3 establishes subsets of animals for age‐related studies and may be used to monitor horses for abnormally high IGF‐1 concentrations due to natural disease or subsequent to systemic growth hormone administration.

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“…Recombinant equine growth hormone (reGH) was first marketed in Australia Ò ) in order to improve the positive nitrogen balance in horses over 15 years (Malinowski et al 1997). However, it is also suspected to be diverted from its original purpose to improve physical performance and wound healing (Dart et al 2003). In this context, the racing rules have strictly prohibited the use of recombinant equine growth hormone in France.…”

Section: Introductionmentioning

confidence: 99%

Generation and processing of urinary and plasmatic metabolomic fingerprints to reveal an illegal administration of recombinant equine growth hormone from LC-HRMS measurements

et al. 2010

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Growth hormones are proteins produced by the anterior pituitary gland responsible for bone and tissue growth through their effects on carbohydrates, lipids and proteins metabolisms. Despite strict regulations banning the use of recombinant equine growth hormone, this substance is suspected to be misused to improve the horse physical performances. In order to check whether the regulation is fulfilled or not, controls are organized and a new analytical screening tool potentially able to detect such abuse was investigated in this paper. An untargeted metabolomics approach, based on liquid chromatography coupled to high resolution mass spectrometry, was developed and applied to characterize and compare horse urinary and plasmatic metabolic profiles upon reGH administrations. After minimal sample preparation, biological fluids were analyzed by LC-ESI(±)-Q-TOF. Data processing was performed by XCMS software and multivariate data analysis applied to the generated data set allowed building OPLS models to discriminate control versus treated populations. Results demonstrated significant metabolic modifications consecutively to the reGH treatment. A comparative study between urinary and plasmatic signatures was performed to evaluate the resulting metabolomic models and to asses their respective interests in the scope of real application for screening reGH administration.

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Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses

Cited by 15 publications

References 25 publications

Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid

Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid

Age‐related changes in serum insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐3 and articular cartilage structure in Thoroughbred horses

Generation and processing of urinary and plasmatic metabolomic fingerprints to reveal an illegal administration of recombinant equine growth hormone from LC-HRMS measurements

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