Clinical implications of macrophage dysfunction in the development of osteoarthritis of the knee

Abstract

Osteoarthritis (OA) is the most common form of arthritic disease, leading to disability and impaired quality of life and no curative treatments exist. Increasing evidence indicates that low-grade inflammation plays a pivotal role in the onset and progression of OA. In this review, we summarize emerging findings on the pathological roles of synovial macrophages, adipose tissue macrophages, and osteoclasts in OA and their potential clinical implications from cell biology to preclinical and preliminary clinical trials. The failure of synovial macrophages to transition from pro-inflammatory M1 to anti-inflammatory M2 subtypes may contribute to the initiation and maintenance of synovitis in OA. M1 macrophages promote the inflammatory microenvironment and progression of OA through interactions with synovial fibroblasts and chondrocytes, thus increasing the secretion of matrix metalloproteinases. Direct inhibition of M1 or promotion of M2 polarization may be useful therapeutic interventions. Adipose tissue macrophages present in the infrapatella fat pad (IPFP) were involved in the progression of obesity-induced OA, which contributed to changes in the integrity of the IPFP. Furthermore, macrophages and osteoclasts in the subchondral bone were involved in bone remodeling and pain through uncoupled osteoclast/osteoblast activity and increased nociceptive signaling. Growing evidence has indicated an important role for macrophage-mediated low-grade inflammation in OA. Fully understanding the link between macrophages and other cells in joints will provide new insights into OA disease modification.