Osteoclasts secrete leukemia inhibitory factor to promote abnormal bone remodeling of subchondral bone in osteoarthritis

Autor: Xin Zhao, Long Ma, Haohui Guo, Jian Wang, Shuai Zhang, Xiaochun Yang, Lvlin Yang, Qunhua Jin
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Musculoskeletal Disorders, Vol 23, Iss 1, Pp 1-12 (2022)
Druh dokumentu: article
ISSN: 1471-2474
DOI: 10.1186/s12891-021-04886-2
Popis: Abstract Background Osteoarthritis (OA) is a common chronic degenerative joint disease. At present, there is no effective treatment to check the progression of osteoarthritis. Osteochondral units are considered to be one of the most important structures affecting the occurrence and development of osteoarthritis. Osteoclasts mediate an increase in abnormal bone remodeling in subchondral bone in the early stage of osteoarthritis. Here, alendronate (ALN) that inhibit osteoclasts was used to study the regulatory effect of osteoclast-derived leukemia inhibitory factor (LIF) on early abnormal bone remodeling. Methods This study involved 10-week-old wild-type female C57BL/6 mice and female SOST knockout (KO) mice that were divided into the sham, vehicle, ALN, and SOST KO groups. Results The expression of LIF was found to decrease by inhibiting osteoclasts, and the histological OA score suggested that the degeneration of articular cartilage was attenuated. Additionally, micro-CT showed that osteoclasts inhibited in the early stage of OA could maintain the microstructure of the subchondral bone. The parameters of bone volume fraction (BV/TV), subchondral bone plate thickness (SBP.Th), and trabecular separation (Tb.Sp) of the treated group were better than those of the vehicle group. Conclusions These results suggested that downregulating the expression of sclerostin in osteocytes by secreting LIF from osteoclasts, activate the Wnt/β-catenin signaling pathway, and promote abnormal bone remodeling in OA. Therefore, clastokine LIF might be a potential molecular target to promote abnormal bone remodeling in early OA.
Databáze: Directory of Open Access Journals
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