Heterotopic Ossification: Basic-Science Principles and Clinical Correlates

Ranganathan, Kavitha; Loder, Shawn; Agarwal, Shailesh; Wong, Victor W.; Forsberg, Jonathan A.; Davis, Thomas A.; Wang, Stewart; James, Aaron W.; Lévi, Benjamin

doi:10.2106/jbjs.n.01056

Cited by 318 publications

(233 citation statements)

References 112 publications

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“…HO represents a major health burden to the patient, associated with pain, mobility impairments, deep vein thrombosis, nerve entrapment, and poor wound healing. Reports of disability associated with HO are variable, but may exceed a frequency of 20%, owing to soft-tissue loss, joint contracture, and chronic pain(8). …”

Section: Introductionmentioning

confidence: 99%

Vascular patterning in human heterotopic ossification

et al. 2017

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Heterotopic ossification (HO, also termed myositis ossificans) is the formation of extra-skeletal bone in muscle and soft tissues. HO is a tissue repair process gone awry, and is a common complication of surgery and traumatic injury. Medical strategies to prevent and treat HO fall well short of addressing the clinical need. Better characterization of the tissues supporting HO is critical to identifying therapies directed against this common and sometimes devastating condition. The physiologic processes of osteogenesis and angiogenesis are highly coupled and interdependent. However, little efforts have been made to document the vascular patterning within heterotopic ossification. Here, surgical pathology case files of 29 human HO specimens were examined by vascular histomorphometric analysis. Results demonstrate a temporospatial patterning of HO vascularity that depends on the ‘maturity’ of the bony lesion. In sum, human HO demonstrates a time and space dependent pattern of vascularization suggesting a coupled pathophysiologic process involving the coordinate processes of osteogenesis and angiogenesis. Further imaging studies may be used to further characterize vasculogenesis within HO and whether anti-angiogenic therapies are a conceivable future therapy for this common condition.

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Section: Introductionmentioning

confidence: 99%

Vascular patterning in human heterotopic ossification

et al. 2017

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“…1 Although HO can arise from fibrodysplasia ossificans progressiva (FOP), HO is typically found following fractures and dislocations, burns, traumatic brain injury and operative procedures. 2 HO often appears within the soft tissue surrounding the joints, leading to joint stiffness, nerve entrapment and persistent pain.…”

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confidence: 99%

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

Liu

et al. 2016

Cell Death Dis

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Emerging evidence has indicated that dysregulated microRNAs (miRNAs) have an important role in bone formation. However, the pathophysiological role of miRNAs in traumatic heterotopic ossification (HO) remains to be elucidated. Using gene expression profile analyses and subsequent confirmation with real-time PCR assays, we identified the decreased expression of miRNA-203 (miR-203) and increased expression of Runx2 as responses to the development of traumatic HO. We found that miR-203 expression was markedly higher in primary and recurrent HO tissues than in normal bones. The upregulation of miR-203 significantly decreased the level of Runx2 expression, whereas miR-203 downregulation increased Runx2 expression. Mutation of the putative miR-203-binding sites in Runx2 mRNA abolished miR-203-mediated repression of Runx2 3'-untranslated region luciferase reporter activity, indicating that Runx2 is an important target of miR-203 in osteoblasts. We also found that miR-203 is negatively correlated with osteoblast differentiation. Furthermore, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-203 and decreased by agomir-203. We showed that miR-203 suppresses osteoblast activity by inhibiting the β-catenin and extracellular signal-regulated kinase pathways. Moreover, using a tenotomy mouse HO model, we found an inhibitory role of miR-203 in regulating HO in vivo; pretreatment with antagomiR-203 increased the development of HO. These data suggest that miR-203 has a crucial role in suppressing HO by directly targeting Runx2 and that the therapeutic overexpression of miR-203 may be a potential strategy for treating traumatic HO.

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“…In other words, it is postulated that there is an imbalance of pro-osteoinductive and anti-osteoinductive mediators located in the soft tissues [9]. Another theory is that cell-mediated interactions with the local tissue environment (which are affected by pH, oxygen amount, availability of micronutrients, and mechanic stimuli) lead to conversion of progenitor precursor cells to osteogenic precursor cells, and, as a result, HO occurs [10].…”

Section: Discussionmentioning

confidence: 99%

Non-Traumatic Intracranial Heterotopic Ossification: A Case from Turkey

Kokaçya¹,

Gökçe²,

Tas³

et al. 2016

FMAR

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Heterotopic ossification (HO) is the abnormal, non-neoplastic presence of lamellar bone in soft tissue. The ectopic formation of lamellar bone in non-osseus tissues secondary to traumatic injuries of the spinal cord or the brain is defined as Neurogenic HO. The pathophysiology of HO is not clear. But several theories like overactive humoral mechanisms after fracture healing, imbalance of pro-osteoinductive and anti-osteoinductive mediators located on the soft tissues and gene mutations in such as bone morphogenetic proteins-4 (BMP-4) are proposed. Casualty factors leading to increased risk of HO include older age, blast mechanism of injury, location of injury and traumatic brain injury. The aim of this paper is to demonstrate a case of HO located in the brain without history of trauma or any other risk factors.

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Heterotopic Ossification: Basic-Science Principles and Clinical Correlates

Cited by 318 publications

References 112 publications

Vascular patterning in human heterotopic ossification

Vascular patterning in human heterotopic ossification

miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2

Non-Traumatic Intracranial Heterotopic Ossification: A Case from Turkey

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