ArticleBone & joint research2017
Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear.
Article in Bone & joint research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation.American journal of physiology. Cell physiology · 2024Article
- Translational therapy from preclinical animal models for muscle degeneration after rotator cuff injury.Journal of orthopaedic translation · 2022Review
- MicroRNA-29a Mitigates Subacromial Bursa Fibrosis in Rotator Cuff Lesion with Shoulder Stiffness.International journal of molecular sciences · 2019Article
- Hypoxia-inducible factor 1α (HIF-1α) is a major determinant in the enhanced function of muscle-derived progenitors from MRL/MpJ mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Fatty Infiltration Is a Prognostic Marker of Muscle Function After Rotator Cuff Tear.The American journal of sports medicine · 2018Article
- A Transgenic tdTomato Rat for Cell Migration and Tissue Engineering Applications.Tissue engineering. Part C, Methods · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesRotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.
methodsChronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.
resultsAt two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons.
conclusionsGSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred.Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J. Russell, C. L. Mendias. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear. Bone Joint Res 2017;6:57-65. DOI: 10.1302/2046-3758.61.BJR-2016-0232.R1.
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