Evaluation of the Cellular Origins of Heterotopic Ossification

Abstract

Heterotopic ossification (HO), acquired or hereditary, is featured by the formation of bone outside of the normal skeleton. Typical acquired HO is a common, debilitating condition associated with traumatic events. Cardiovascular calcification, an atypical form of acquired HO, is prevalent and associated with high rates of cardiovascular mortality. Hereditary HO syndromes, such as fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, are rare, progressive, life-threatening disorders. The cellular origins of HO remain elusive. Some bona fide contributing cell populations have been found through genetic lineage tracing and other experiments in vivo, and various other candidate populations have been proposed. Nevertheless, because of the difficulties in establishing cellular phenotypes in vivo and other confounding factors, the true identities of these populations are still uncertain. This review critically evaluates the accumulating data in the field. The major focus is on the candidate populations that may give rise to osteochondrogenic lineage cells directly, not the populations that may contribute to HO indirectly. This issue is important not solely because of the clinical implications, but also because it highlights the basic biological processes that govern bone formation.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

“…Cells from several origins have been proposed to be implicated in the formation of ectopic bones in traumatic or hereditary HOs (14). First, circulating osteogenic precursors have been reported to contribute to HO formation in patients with FOP (15), confirming a previous report in a mouse model in which ectopic ossification was induced by collagen implants containing exogenous recombinant BMP-2 (16).…”

Pathogenesis and prevention strategies of heterotopic ossification in total hip arthroplasty: a narrative literature review and results of a survey in Germany

“…The surrounding soft tissue should be carefully cleaned (drained) during THA. Kan and Kessler (2014) argued in a recent, detailed review on the cellular origins of HO that, according to current data, cells of mesoderm origin seem to be the main direct contributors to HO formation as they are capable of differentiating into osteolineage cells. Ectodermal (i.e.…”

Pseudomalignant myositis ossificans in the breast: A case report

“…Due to the presence of bone formation as well as a similar epidemiology, osteosarcoma needs to be excluded. An important feature is the characteristic zonation in myositis ossificans, which is in contrast to the lace-like disorderly growth of osteoid bone formations in osteosarcomas (5,14). Small biopsies can be difficult to interpret since zonation is usually not present (14).…”

“…The pathophysiology of MO formation is incompletely understood. Kan et al (5) demonstrated that the cellular mechanism of heterotopic bone formation is the result of local stem cell dysregulation in response to tissue injury and subsequent inflammation. Recent studies have demonstrated that extra-skeletal bone formation may be dependent on a process known as endothelial-mesenchymal transition (4,5).…”

“…Patients may present atypically, especially when the history is not clear. This atypical clinical presentation, combined with nonspecific imaging findings, often raises concerns of malignancy (4)(5)(6). MO often starts as a non-specific painful soft tissue mass that could be mistaken for an infection or a soft tissue tumor.…”