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We undertook this study to characterize the joint pathology of mice with overexpression of bovine GH (\n                      <jats:italic>bGH<\/jats:italic>\n                      ) or a GH receptor antagonist (\n                      <jats:italic>GHa<\/jats:italic>\n                      ) and to investigate the effect of GH on regulation of chondrocyte cellular metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Knee joints from mice overexpressing\n                      <jats:italic>bGH<\/jats:italic>\n                      or\n                      <jats:italic>GHa<\/jats:italic>\n                      and wild\u2010type (WT) control mice were examined using histology and micro\u2013computed tomography for osteoarthritic (OA) pathologies. Additionally, cartilage from\n                      <jats:italic>bGH<\/jats:italic>\n                      mice was used for metabolomics analysis. Mouse primary chondrocytes from\n                      <jats:italic>bGH<\/jats:italic>\n                      and WT mice, with or without pegvisomant treatment, were used for quantitative polymerase chain reaction and Seahorse respirometry analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both male and female\n                      <jats:italic>bGH<\/jats:italic>\n                      mice at ~13 months of age had increased knee joint degeneration, which was characterized by loss of cartilage structure, expansion of hypertrophic chondrocytes, synovitis, and subchondral plate thinning. The joint pathologies were also demonstrated by significantly higher Osteoarthritis Research Society International and Mankin scores in\n                      <jats:italic>bGH<\/jats:italic>\n                      mice compared to WT control mice. Metabolomics analysis revealed changes in a wide range of metabolic pathways in\n                      <jats:italic>bGH<\/jats:italic>\n                      mice, including beta\u2010alanine metabolism, tryptophan metabolism, lysine degradation, and ascorbate and aldarate metabolism. Also,\n                      <jats:italic>bGH<\/jats:italic>\n                      chondrocytes up\u2010regulated fatty acid oxidation and increased expression of\n                      <jats:italic>Col10a<\/jats:italic>\n                      . Joints of\n                      <jats:italic>GHa<\/jats:italic>\n                      mice were remarkably protected from developing age\u2010associated joint degeneration, with smooth articular joint surface.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study showed that an excessive amount of GH promotes joint degeneration in mice, which was associated with chondrocyte metabolic dysfunction and hypertrophic changes, whereas antagonizing GH action through a GHa protects mice from OA development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42470","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T03:21:17Z","timestamp":1675999277000},"page":"1139-1151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Promotion of Joint Degeneration and Chondrocyte Metabolic Dysfunction by Excessive Growth Hormone in Mice"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-1504","authenticated-orcid":false,"given":"Shouan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University  Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University  Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Davis","sequence":"additional","affiliation":[{"name":"Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University  Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig R. G.","family":"Willis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, Athens, and School of Chemistry and Biosciences, Faculty of Life Sciences University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reetobrata","family":"Basu","sequence":"additional","affiliation":[{"name":"Edison Biotechnology Institute Ohio University  Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Witzigreuter","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Ohio University  Athens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Bell","sequence":"additional","affiliation":[{"name":"Edison Biotechnology Institute Ohio University  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