Heterotopic ossification (HO) is defined as the occurrence of extraskeletal bone in soft tissue. Although this pathological osteogenesis process involves the participation of osteoblasts and osteoclasts during the formation of bone structures, it differs from normal physiological osteogenesis in many features. In this article, the primary characteristics of heterotopic ossification are reviewed from both clinical and basic research perspectives, with a special highlight on the influence of mechanics on heterotopic ossification, which serves an important role in the prophylaxis and treatment of HO.

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A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.