Vascular patterning in human heterotopic ossification

Abstract

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.

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

“…34,47 When stimulated with BMP2, this cell line is useful in the study of osteogenic differentiation and particularly in the context of HO. 18,39,[52][53][54][55][56][57] Whilst the mechanistic insight from this cellular model has been valuable, this approach also has limitations. It recapitulates a single cell of origin picture of acquired HO that is known to be complex and involving the interaction of multiple cell types of different embryonal lineages, and the dominant initiating cell type remains unknown.…”

Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification

“…Although HO can form in diverse anatomic sites, including tendon, ligament, and muscle, it consistently derives from tissue-resident connective tissue mesenchymal progenitor cells (1,(3)(4)(5)(6). Here, predominantly local stromal/fibroblastic cells of mesenchymal origin within connective tissue (3,4,(6)(7)(8) undergo abnormal osteochondral differentiation producing pathologic extracellular matrix of bone and cartilage (1,9).…”

Effects of hydrogen peroxide on biological characteristics and osteoinductivity of decellularized and demineralized bone matrices

“…The IHC staining of VEGF in two materials was also performed in this study due to its capability of enhancing the calcification. A coupled process that caused by the coordination of angiogenesis and osteogenesis could lead to the formation of new bone and HO . Moreover, TGF‐β1 and BMP‐2 could exhibit a strong synergistic activity for promoting the bone formation and ectopic calcification .…”

“…A coupled process that caused by the coordination of angiogenesis and osteogenesis could lead to the formation of new bone and HO. 35 Moreover, TGF-β1 and BMP-2 could exhibit a strong synergistic activity for promoting the bone formation and ectopic calcification. 36 In this study, both of the two materials displayed the negative staining of VEGF and TGF-β1.…”