Distraction osteogenesis, or the Illizarov technique, induces bone regeneration using distractive mechanical forces. Nevertheless, Wolff’s law holds that bone adapts to reverse compressive mechanical loads, growing denser in areas of high pressure and resorbing in zones of low pressure. These two forms of new bone formation together suggest that mechanical stimuli play an important role in bone remodeling and regeneration. The therapeutic efficacy of distraction osteogenesis has been recognized in orthopedics and maxillofacial surgeries. Distraction osteogenesis was even used for the regeneration of various other tissues/organs, such as blood vessels and skin (e.g., in the treatment of limb ischemic diseases and foot ulcers), suggesting the principle of distraction histogenesis. However, the underlying mechanisms, particularly those of the cross-organ effects and in terms of mechanotransduction, remain poorly understood. Thus, this review aims to explore the recent advances in research on musculoskeletal regeneration and its association with mechanosensitive channels from a new interdisciplinary application perspective. The contents can provide insights into potential research directions for understanding the molecular mechanisms of musculoskeletal regeneration and its clinical applications.

Osteoarthritis (OA) is a debilitating chronic joint disease affecting large populations of patients, especially the elderly. The pathological mechanisms of OA are currently unknown. Multiple risk factors are involved in OA development. Among these risk factors, alterations of mechanical loading in the joint leading to changes in biological signaling pathways have been known as a key event in OA development. The importance of AMPK-β-catenin-Runx2 signaling in the initiation and progression of OA has been recognized in recent years. In this review, we discuss the recent progress in understanding the role of this signaling pathway and the underlying interaction mechanisms during OA development. We also discuss the drug development aiming to target this signaling pathway for OA treatment.

Although aging has traditionally been viewed as the most important risk factor for osteoarthritis (OA), an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA, particularly in younger individuals. Metabolic abnormalities, such as obesity and type Ⅱ diabetes, are strongly linked to OA, and they affect both weight-bearing and non-weight-bearing joints, thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight. This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk, including the impact of abnormal glucose and lipid metabolism, the potential pathogenesis and targeted therapeutic strategies.