Parathyroid hormone ameliorates temporomandibular joint osteoarthritic‐like changes related to age

Abstract

Objectives Ageing could be a contributing factor to the progression of temporomandibular joint osteoarthritis (TMJ OA), whereas its pathogenesis and potential therapeutic strategy have not been comprehensively investigated. Materials and methods We generated ageing mouse models (45‐week and 60‐week; 12‐week mice as control) and intermittently injected 45‐week mice with parathyroid hormone (PTH(1‐34)) or vehicle for 4 weeks. Cartilage and subchondral bone of TMJ were analysed by microCT, histological and immunostaining. Western blot, qRT‐PCR, ChIP, ELISA and immunohistochemical analysis were utilized to examination the mechanism of PTH(1‐34)’s function. Results We showed apparent OA‐like phenotypes in ageing mice. PTH treatment could ameliorate the degenerative changes and improve bone microarchitecture in the subchondral bone by activating bone remodelling. Moreover, PTH inhibited phosphorylation level of Smad3, which can combine with p16ink4a gene promoter region, resulting in reduced senescent cells accumulation and increased cellular proliferation of marrow mesenchymal stem cells (MSCs). ELISA also showed relieved levels of specific senescent‐associated secretory phenotype (SASP) in ageing mice after PTH treatment. Conclusions In summary, PTH may reduce the accumulation of senescent cells in subchondral bone by inhibiting p16ink4a and improve bone marrow microenvironment to active bone remodelling process, indicating PTH administration could be a potential preventative and therapeutic treatment for age‐related TMJ OA.

Parathyroid hormone attenuates osteoarthritis pain by remodeling subchondral bone in mice

“…The parathyroid gland, the main production site of PTH, evolved in amphibians and supported the transition from aquatic to terrestrial life, allowing terrestrial locomotion in previously aquatic vertebrates (26). PTH prevents cartilage degeneration and/or the deterioration of subchondral bone (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), induces cartilage regeneration or chondrocytes proliferation in osteoarthritis (27,38), and stimulates subchondral bone and articular cartilage repair of focal osteochondral defects (28). PTH also interacts with local osteotropic factors to orchestrate the coupling of bone resorption and formation in an anabolic signaling network (25,39), and PTH and TGF-β work in concert to exert their physiological activities in bone (25).…”

Causal Relationship Between Parathyroid Hormone and the Risk of Osteoarthritis: A Mendelian Randomization Study

“…These improvements were likely caused by reduced chondrocyte terminal differentiation and apoptosis as well as increased autophagy. Furthermore, PTH may inhibit p16 ink4a , a cyclin-dependent kinase inhibitor and senescence biomarker, resulting in the decreased accumulation of senescent cells in subchondral bone and an improved bone marrow microenvironment to stimulate the process of bone remodeling ( Cui et al, 2020 ). However, there has been little human data on this issue, with a cross-sectional study including 5,880 Korean participants who demonstrated that although there was a trend for a negative association in women, no statistically significant association was found between endogenous PTH and knee OA ( Lee, 2016 ).…”

The Relationship Of Myogenic Temporomandibular Disorders With Depression And Health-Related Quality Of Life In Non-Dialysis Chronic Kidney Disease

“…In the study of Nilsson IM et al, the frequency of TMD in adolescents was higher than in adults (29). In the study of Cui C. et al age was shown to be a risk factor for TMD (30). Advanced age has been considered as a risk factor for depression in the study of Al-Jabi SW et al with hemodialysis patients (28).…”