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dc.contributor.authorZhu, S.
dc.contributor.authorLiu, H.
dc.contributor.authorDavis, T.
dc.contributor.authorWillis, Craig R.G.
dc.contributor.authorBasu, R.
dc.contributor.authorWitzigreuter, L.
dc.contributor.authorBell, S.
dc.contributor.authorSzewczyk, N.
dc.contributor.authorLotz, M.K.
dc.contributor.authorHill, M.
dc.contributor.authorFajardo, R.J.
dc.contributor.authorO'Connor, P.M.
dc.contributor.authorBerryman, D.E.
dc.contributor.authorKopchick, J.J.
dc.date.accessioned2023-04-03T10:48:24Z
dc.date.accessioned2023-04-12T14:09:13Z
dc.date.available2023-04-03T10:48:24Z
dc.date.available2023-04-12T14:09:13Z
dc.date.issued2023-07
dc.identifier.citationZhu S, Liu H, Davis T et al (2023) Promotion of joint degeneration and chondrocyte metabolic dysfunction by excessive growth hormone in mice. Arthritis & Rheumatology. 75(7): 1139-1151.en_US
dc.identifier.urihttp://hdl.handle.net/10454/19398
dc.descriptionYesen_US
dc.description.abstractObjective: Many patients with acromegaly, a hormonal disorder with excessive growth hormone (GH) production, report pain in joints. We undertook this study to characterize the joint pathology of mice with overexpression of bovine GH (bGH) or a GH receptor antagonist (GHa) and to investigate the effect of GH on regulation of chondrocyte cellular metabolism. Methods: Knee joints from mice overexpressing bGH or GHa and wild-type (WT) control mice were examined using histology and micro–computed tomography for osteoarthritic (OA) pathologies. Additionally, cartilage from bGH mice was used for metabolomics analysis. Mouse primary chondrocytes from bGH and WT mice, with or without pegvisomant treatment, were used for quantitative polymerase chain reaction and Seahorse respirometry analyses. Results: Both male and female bGH 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 bGH mice compared to WT control mice. Metabolomics analysis revealed changes in a wide range of metabolic pathways in bGH mice, including beta-alanine metabolism, tryptophan metabolism, lysine degradation, and ascorbate and aldarate metabolism. Also, bGH chondrocytes up-regulated fatty acid oxidation and increased expression of Col10a. Joints of GHa mice were remarkably protected from developing age-associated joint degeneration, with smooth articular joint surface. Conclusion: 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.en_US
dc.description.sponsorshipDr. Zhu's work was supported by Ohio University, the Arthritis National Research Foundation (grant 833836), a FIRST award from the American Society for Bone and Mineral Research, the NIH (grant R15-AR-080813), and a Hevolution Foundation AGE grant (AGE-008). Dr. Davis’ work was supported by a medical student seed grant from Ohio University. Dr. Lotz's work was supported by the NIH (grant R37-AG-059418). Dr. Berryman was supported by the NIH (grant R01-AG-059779). Dr. Kopchick was supported by the State of Ohio's Eminent Scholar Program that includes a gift from Milton and Lawrence Goll and the AMVETS, and by the NIH (grant R01-AG-059779).
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1002/art.42470en_US
dc.rights© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.en_US
dc.subjectExcessive growth hormoneen_US
dc.subjectJoint degenerationen_US
dc.subjectChondrocyte metabolic dysfunctionen_US
dc.subjectMiceen_US
dc.titlePromotion of joint degeneration and chondrocyte metabolic dysfunction by excessive growth hormone in miceen_US
dc.status.refereedYesen_US
dc.date.Accepted2023-02-02
dc.date.application2023-02-10
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.rights.licenseCC-BY-NCen_US
dc.date.updated2023-04-03T10:48:26Z
refterms.dateFOA2023-04-12T14:10:01Z
dc.openaccess.statusopenAccessen_US


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