Heterotopic ossification: a review

McCarthy, Edward F.; Sundaram, Murali

doi:10.1007/s00256-005-0958-z

Cited by 323 publications

(250 citation statements)

References 56 publications

Supporting

Mentioning

237

Contrasting

Unclassified

Order By: Relevance

“…Postnatal bone formation is normally restricted to the skeleton during fracture healing; however, heterotopic ossification (HO) can occur at extraskeletal sites, frequently in response to severe tissue trauma (Kaplan et al 2004;McCarthy and Sundaram 2005;Evans et al 2014). In a rare genetic form of HO, FOP, ectopic endochondral ossification forms episodically and progressively at extraskeletal sites within soft connective tissue, including skeletal muscle, fascia, tendon, and ligaments, resulting in severe disability (Kaplan et al 2008a;Kaplan 2008, 2010).…”

Section: Heterotopic Ossification Caused By Dysregulation Of Bmp Signmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

show abstract

Section: Heterotopic Ossification Caused By Dysregulation Of Bmp Signmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

show abstract

“…However, despite continued efforts to identify the cellular and molecular events leading to HO, the mechanisms of pathogenesis continue to remain elusive. To date many contributory biological factors have been implicated in the etiology (see diagram 1), including the bone morphogenetic proteins (BMPs), inflammation, prostaglandin E2, hypercalcemia, hypoxia, abnormal nerve activity, immobilization and dysregulation of hormones [1,24]. However, in addition to the biological contribution, HO is also associated with a change in local biomechanics, as can be observed following reparative surgeries, such as cervical total disc replacement, where resulting changes in height of the functional segmental unit or increases in range of motion may influence the formation of HO [25].…”

Section: Pathogenesismentioning

confidence: 99%

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

et al. 2015

View full text Add to dashboard Cite

“…[1][2][3][4][5][6][7][8][9] These contexts, normal or otherwise, share fundamental characteristics at many levels, including molecular (overexpression of bone morphogenic proteins, BMPs), cellular (a set of progenitor cells that commits to an osteoblastic lineage) and biomechanical (translation of the mechanical forces into structured and organized bone). [3,[10][11][12][13][14][15] However, there are still significant gaps in our understanding of these events and in particular few models allow long-term Bone is a dynamic tissue that remodels continuously in response to local mechanical and chemical stimuli. This process can also result in maladaptive ectopic bone in response to injury, yet pathological differences at the molecular and structural levels are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

et al. 2017

View full text Add to dashboard Cite

Bone is a dynamic tissue that remodels continuously in response to local mechanical and chemical stimuli. This process can also result in maladaptive ectopic bone in response to injury, yet pathological differences at the molecular and structural levels are poorly understood. A number of in vivo models exist but can often be too complex to allow isolation of factors which may stimulate disease progression. A self‐structuring model of bone formation is presented using a fibrin gel cast between two calcium phosphate ceramic anchors. Femoral periosteal cells, seeded into these structures, deposit an ordered matrix that closely resembles mature bone in terms of chemistry (collagen:mineral ratio) and structure, which is adapted over a period of one year in culture. Raman spectroscopy and X‐ray diffraction confirm that the mineral is hydroxyapatite associated with collagen. Second‐harmonic imaging demonstrates that collagen is organized similarly to mature mouse femora. Remarkably, cells differentiated to the osteocyte phase are linked by canaliculi (as demonstrated with nano‐computed tomography) and remained viable over the full year of culture. It is demonstrated that novel drugs can prevent ossification in constructs. This model can be employed to study bone formation in an effort to encourage or prevent ossification in a range of pathologies.

show abstract

Heterotopic ossification: a review

Cited by 323 publications

References 56 publications

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network

Contact Info

Product

Resources

About