Advances on T cell immunity in bone remodeling and bone regeneration.

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Abstract

[Indexed for MEDLINE] Conflict of interest statement: 所有作者均声明不存在利益冲突 The authors declare that there is no conflict of interests 11. J Orthop Res. 2025 Nov;43(11):1973-1986. doi: 10.1002/jor.70040. Epub 2025 Aug 3. COX-2 in Fracture Callus Chondro-Osseous Junction Osteoclasts Regulates Chondrocyte Hypertrophy and Callus Vasculogenesis. Teitelbaum M(1)(2), Lin HN(1)(2)(3), Culbertson MD(1), Wetterstrand C(1), Patrick O'Connor J(1)(2). Author information: (1)Department of Orthopaedics, Rutgers-New Jersey Medical School, Newark, New Jersey, USA. (2)Rutgers-School of Graduate Studies, Newark Health Sciences Campus, Newark, New Jersey, USA. (3)Eli Lilly and Company, New York, New York, USA. Cyclooxygenase-2 (COX-2) activity is necessary for bone fracture healing to proceed normally. COX-2 is encoded by Ptgs2 and is expressed by several cell types during fracture healing, suggesting that COX-2 regulates multiple processes to affect fracture healing. Here, the role of COX-2 expression in osteoclasts during mouse femur fracture healing was examined. Mice lacking COX-2 (Ptgs2-cKOLyz2) in osteoclasts and other myeloid cells were made using a floxed COX-2 gene (Ptgs2tm1Hahe) and cre recombinase expressed from the Lyz2tm1(cre)If° allele. Fracture healing was assessed by radiology, histology, immunohistochemistry, and mRNA quantification. Targeted loss of COX-2 in osteoclasts was confirmed by immunohistochemistry and led to significant reductions in callus osteoclasts. Comparisons between Ptgs2-cKOLyz2 and control mice found significant reductions in callus chondrogenesis and bone formation in the Ptgs2-cKOLyz2 mice. The reductions were accompanied by delayed callus vascularization and reduced MMP-13 expression. Immunohistochemistry showed that osteoclasts along the callus chondro-osseous junction normally express COX-2. In Ptgs2-cKOLyz2 mice, COX-2 expression was reduced in osteoclasts at the chondro-osseous junction and coincided with reduced MMP-13 expression at the chondro-osseous junction. The results indicate that COX-2 expressed by osteoclasts along the chondro-osseous junction promotes vasculogenesis and regulates chondrocyte hypertrophy during endochondral ossification. The results also indicate that osteoclasts at the callus chondro-osseous junction coordinate multiple cellular processes to promote endochondral ossification. © 2025 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society. DOI: 10.1002/jor.70040 PMCID: PMC12509252