Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

Abstract

Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre‐osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/β‐catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.

Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition

“…In this regard, both osteoporosis and knee OA are attributed to menopause 32 , 33 . However, the possibility of osteoporosis causing the development of knee OA is uncertain.…”

Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR‐214‐3p from bone marrow‐derived mesenchymal stem cells

“…After finishing the right knee loading, the same loading procedure was conducted on the left knee. 16 The sham control and OVX groups received sham loading, in which mice were positioned on the loading table without receiving dynamic loading to the knee. In the current study, loads with 1 N and 5 Hz were given for 6 min/day for 14 consecutive days.…”

“…12 Mechanical forces play a crucial role in vascular injury and repair, which can directly activate the mechanosensing molecules. 13 We have developed joint loading modalities, 14 in which dynamic lateral loads are applied to synovial joints such as the elbow, 15 knee, 16 and ankle. 17,18 It is considered that mechanical loading induces dynamic deformation in the epiphysis that drives the alteration in intramedullary pressure in the medullary cavity and interstitial fluid flow in the lacunocanalicular network.…”

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

“…Osteoarthritis (OA), one of the most severe pathologic changes that often occurs in the temporomandibular joints (TMJs) of patients with temporomandibular disorders, is mainly characterized by progressive cartilage degradation and subchondral bone changes (Glyn-Jones et al 2015). Recent studies have shown that bone marrow mesenchymal stem cells (BMSCs) in the subchondral bone of OA joints release a variety of proteins to exacerbate OA progression (Jiao, Niu, Li, et al 2015; Yang et al 2015; Zheng et al 2020). These studies demonstrated that BMSCs of the subchondral bone play an important pathogenic role during OA progression (Zhen et al 2013; Sun et al 2020); however, the exact pathologic mechanism remains unclear.…”