**Łukasz Pulik 1,**†**, Bartosz Mierzejewski 2,**†**, Maria A. Ciemerych 2, Edyta Brzóska 2,\* and Paweł Ł ˛egosz 1,\***


Received: 17 April 2020; Accepted: 21 May 2020; Published: 26 May 2020

**Abstract:** Heterotopic ossification (HO) manifests as bone development in the skeletal muscles and surrounding soft tissues. It can be caused by injury, surgery, or may have a genetic background. In each case, its development might differ, and depending on the age, sex, and patient's conditions, it could lead to a more or a less severe outcome. In the case of the injury or surgery provoked ossification development, it could be, to some extent, prevented by treatments. As far as genetic disorders are concerned, such prevention approaches are highly limited. Many lines of evidence point to the inflammatory process and abnormalities in the bone morphogenetic factor signaling pathway as the molecular and cellular backgrounds for HO development. However, the clear targets allowing the design of treatments preventing or lowering HO have not been identified yet. In this review, we summarize current knowledge on HO types, its symptoms, and possible ways of prevention and treatment. We also describe the molecules and cells in which abnormal function could lead to HO development. We emphasize the studies involving animal models of HO as being of great importance for understanding and future designing of the tools to counteract this pathology.

**Keywords:** muscles; heterotopic ossification; skeletal muscle stem and progenitor cells; HO precursors
