Autonomic nervous regulation of cellular processes during subchondral bone remodeling in osteoarthritis

Osteoarthritis (OA) is the most prevalent degenerative joint disease. Besides loss of articular cartilage and synovial inflammation, OA progression is characterized by pathological changes in the subchondral bone. In early OA, subchondral bone remodeling typically shifts to an increased bone resorption. However, as the disease progresses an increased bone formation takes place, leading to higher bone density with subsequent bone sclerosis. These changes can be influenced by different local or systemic factors. Recent evidence suggests that the autonomic nervous system (ANS) plays a role in regulating subchondral bone remodeling in OA. In this review, we 1) introduce bone structure and cellular mechanisms of bone remodeling in general, 2) explain the subchondral bone changes during OA pathogenesis, 3) then describe the contribution of the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS), the two major autonomic branches, to physiological subchondral bone remodeling, 4) followed by the influence of the SNS and PNS on subchondral bone remodeling in OA, and 5) finally, discuss the potential of therapeutic approaches targeting different components of the ANS.