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

FASEB J. 2020 Feb;34(2):3399-3412. doi: 10.1096/fj.201902117R. Epub 2020 Jan 10.

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.

Keywords: Wnt signaling; knee loading; osteoblast; osteoclast; osteoporotic osteoarthritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cell Adhesion
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrocytes / physiology
  • Female
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism
  • Osteoarthritis / therapy*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoblasts / physiology
  • Osteoporosis, Postmenopausal / complications
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / therapy*
  • Weight-Bearing*
  • Wnt Signaling Pathway*