Contemporary perspectives on heterotopic ossification

Abstract

AWJ reports laboratory research support from MTF Biologics and Novadip. AWJ is a paid consultant for Novadip and LifeSprout. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies.

Development of an Animal Model for Traumatic Brain Injury Augmentation of Heterotopic Ossification in Response to Local Injury

“…There has been a great deal of controversy regarding the exact nature of progenitors for osteoblasts involved in FOP and HO formation. Different sources of osteogenic precursors including mesenchymal stem cells in the bone marrow, pericytes, satellite cells, interstitial cells between muscle fibers, circulating stem cells and nerve stem cells have been proposed [ 22 ]. A common niche for mesenchymal progenitors is the perivascular space, and there is considerable evidence in the literature for regenerative potential of pericytes when applied to bone.…”

Hypoxia Drives Material‐Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid‐Loaded Macrophage Axis

“…[3,4] Under certain circumstances, bone tissue can be formed in non-osseus sites in a process that is known as heterotopic ossification (HO), which can either be a hereditary or acquired disease. [5,6] Among acquired HO, pathological heterotopic bone formation is often seen after musculoskeletal trauma, [7] spinal cord injury, [8] central nervous system injury, [9] atherosclerotic carotid arteries, [10] cardiac valves, [11] and in different types of tumors. [12] Although these occurrences of pathological HO are an undesired clinical complication, controlled bone formation in nonosseous sites can be induced by osteoinductive materials without the help of exogenous growth factors/osteogenic cells.…”

Verteporfin attenuates trauma‐induced heterotopic ossification of Achilles tendon by inhibiting osteogenesis and angiogenesis involvingYAP/β‐catenin signaling

“…Surgical resections are commonly considered an effective treatment for HO, but long‐term efficacies are annoying, with a high rate of HO recurrence 6 . Existing methods of HO prophylaxis include radiotherapy, nonsteroidal anti‐inflammatory drugs, or bisphosphonates 7 ; however, each of these methods can be complicated by either suboptimal efficacy or rare but potentially severe side effects 8 . Therefore, it is urgent for researchers to understand the underlying mechanism driving HO formation and find effective molecules or drugs for HO prophylaxis.…”

“…Several signaling pathways associated with this process have been reported, including the bone morphogenetic protein signaling pathway, hypoxia‐inducible factor pathway, Wnt/β‐Catenin signaling pathway, hedgehog signaling pathway, G‐protein alpha‐subunit signaling pathway, and retinoic acid receptor signaling pathway 2 . Moreover, the process of HO progression requires a significant amount of energy and relies on blood vessels to transport essential nutrients such as glucose, oxygen, amino acids, and minerals needed for osteogenesis, as well as to remove waste generated by osteoclast resorption 7,11 . Type H vessel has been reported to appear in the process of HO formation as an important role in coupling with osteogenesis 12 .…”