Imaging Findings of Metabolic Bone Disease.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 10. Bone Joint Res. 2025 Jul 1;14(7):589-600. doi: 10.1302/2046-3758.147.BJR-2024-0347.R1. G-protein-coupled estrogen receptor-1 facilitates chondrocyte proliferation in pubertal epiphyseal growth plate via PTHrP/Ihh regulation. Chou YS(1)(2), Lin SY(1)(2)(3)(4)(5), Chuang SC(1)(2), Shih PY(1)(2), Chen CH(1)(2)(3)(6)(7)(8)(9), Ho ML(1)(2)(10), Chang JK(1)(2)(3). Author information: (1)Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. (2)Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. (3)Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. (4)Department of Orthopedics, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan. (5)Department of Orthopedics, School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. (6)Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan. (7)School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. (8)PhD Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. (9)Graduate Institute of Materials Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung, Taiwan. (10)Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AIMS: Oestrogen drives long-bone development through various oestrogen receptors. G-protein-coupled oestrogen receptor-1 (GPER-1), a membrane oestrogen receptor, mediates longitudinal bone growth during early puberty; however, the underlying mechanisms remain unclear. Therefore, this study elucidated the mechanisms underlying GPER-1-mediated bone growth. METHODS: A GPER-1 agonist (G1), GPER-1 antagonist (G15), and chondrocyte-specific GPER-1 knockout experiment (Col2a1-Cre; GPER-1f/f, CKO) were used to investigate the role of GPER-1 in growth plate chondrocytes from C57BL/6 mice (total number = 48). We investigated the effects of GPER-1 activation or inhibition on the tibial growth plate and bone growth, including changes in proliferation and hypertrophy, and the expression of parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), and their ratio (PTHrP/Ihh). RESULTS: G1 treatment-induced GPER-1 activation increased tibial growth plate thickness, proliferative zone thickness, and chondrocyte proliferation in mice. The hypertrophic zone thickness and type X collagen-stained area decreased in four-week-old G1-treated mice compared with the control group. GPER-1 activation increased the PTHrP/Ihh ratio in the growth plates of four- and eight-week-old mice. In contrast, blocking or deleting GPER-1 decreased the proliferative zones of the growth plate, proliferative chondrocytes, and PTHrP/Ihh. Additionally, the hyperopic zones of the growth plates increased with GPER-1 deficiency. In vitro micromass-3D cultured chondrocyte studies confirmed that G1 treatment increased proliferation, decreased hypertrophy, and increased PTHrP/Ihh protein levels. CONCLUSION: This study demonstrates that GPER-1 maintains proliferation but suppresses chondrocyte hypertrophy in growth plates by upregulating PTHrP/Ihh during early puberty in male and female mice. Our findings suggest that GPER-1 may serve as a potential target for therapeutic modulation of linear bone growth during puberty. © 2025 Chou et al. DOI: 10.1302/2046-3758.147.BJR-2024-0347.R1 PMCID: PMC12208743