Pathogenesis of acquired heterotopic ossification:​ risk factors, cellular mechanisms, and therapeutic implications

Cao, Guorui<sup>1</sup>; Zhang, Shaoyun<sup>2</sup>; Wang, Yixuan<sup>3</sup>; Quan, Songtao<sup>1</sup>; Yue, Chen<sup>1</sup>; Yao, Junna<sup>1</sup>; Alexander, Peter G.<sup>4</sup>; Tan, Honglue<sup>1</sup>

Affiliations

¹Department of Knee Surgery, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, Henan Province, People’s Republic of China

²Department of Orthopedics, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan Province, People’s Republic of China

³Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China

⁴Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, United States of America

Abstract and keywords

Heterotopic ossification (HO), including hereditary and acquired HO, is the formation of extraskeletal bone in skeletal muscle and surrounding soft tissues. Acquired HO is often caused by range of motion, explosion injury, nerve injury or burns. Severe HO can lead to pain and limited joint activity, affecting functional rehabilitation and quality of life. Increasing evidence shows that inflammatory processes and mesenchymal stem cells (MSCs) can drive HO. However, explicit knowledge about the specific mechanisms that result in HO and related cell precursors is still limited. Moreover, there are no effective methods to prevent or reduce HO formation. In this review, we provide an update of known risk factors and relevant cellular origins for HO. In particular, we focus on the underlying mechanisms of MSCs in acquired HO, which follow the osteogenic program. We also discuss the latest therapeutic value and implications for acquired HO. Our review highlights the current gaps in knowledge regarding the pathogenesis of acquired HO and identifies potential targets for the prevention and treatment of HO.

Keywords: Heterotopic ossification; Risk factors; Stem cells; Macrophage; Treatment

Links

DOI: 10.1016/j.bone.2022.116655

PubMed: 36581258

WoS: 000920483200001

History

Received: 2022-08-7

Revised: 2022-12-14

Accepted: 2022-12-22

Online: 2022-12-26

Cited Works (6)

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Cited By (1)

Year	Entry
2023	Mierzejewski B, Pulik Ł, Grabowska I, Sibilska A, Ciemerych MA, Łęgosz P, Brzoska E. Coding and noncoding RNA profile of human heterotopic ossifications: risk factors and biomarkers. Bone. November 2023;176:116883.