Heterotopic Ossification

Kaplan, Frederick S.; Glaser, David L.; Hebela, Nader M.; Shore, Eileen M.

doi:10.5435/00124635-200403000-00007

Cited by 310 publications

(250 citation statements)

References 33 publications

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“…The development of HO is theorized to require differentiation of mesenchymal progenitor cells toward chondrocyte and osteoblastic lineage, necessary steps for endochondral ossification [25]. As seen in our study, the expression of transcripts necessary for synthesis of cartilaginous matrix (COL2A1, COL10A1, COL11A1, COMP) and tissue remodeling (MMP8, MMP9) were upregulated in wounds in which HO developed.…”

Section: Gene Upregulation In Patients Who Developed Heterotopic Ossisupporting

confidence: 73%

“…Soft tissue injury in the setting of a hyperinflammatory response has been shown to contribute substantially to ectopic skeletogenesis [16,25,32]. Specifically, the expression of BMP-2 and related osteoinductive morphogens by tissue macrophages and other inflammatory mediators is highly Expression values represented as fold change in wounds in which heterotopic ossification (HO) developed compared with control expression values of wounds in which HO did not develop at initial and final surgical débridements.…”

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

“…Differences in gene expression between groups evaluated using the Mann-Whitney U test; ALPL = alkaline phosphatase, COL = collagen alpha, COMP = collagen oligometric matrix protein, CSF = colony stimulating factor, MMP = matrix metalloproteinase; SMAD1 = SMAD family member. upregulated at sites of muscular damage and soft tissue injury [6,25,41]. Overactive BMP signaling has been implicated in the development of HO [25,46,48].…”

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

“…Recurrent mutations in the BMP type-1 receptor, activin receptor IA (ACVR1), and local changes in the expression of BMP-4 and its receptor (BMPR1A) have been linked to the rare genetic disorder fibrodysplasia ossificans progressiva [11,13,18,20,26]. The more common acquired forms of HO frequently occur as a complication of THA, elbow or acetabular fractures requiring surgical treatment, soft tissue injury secondary to trauma or deep muscle dissection, and traumatic brain or spinal cord injuries [3,7,8,25,49].…”

Section: Introductionmentioning

confidence: 99%

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Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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Background Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Conclusions Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds.

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Section: Gene Upregulation In Patients Who Developed Heterotopic Ossisupporting

confidence: 73%

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Section: Functional Protein Expression and Heterotopic Ossificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Evans

Potter

Brown

et al. 2013

Clin Orthop Relat Res

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“…Heterotopic ossification (HO) may occur as a consequence of musculoskeletal trauma from blast and high-energy injuries [2,21,40,52], total joint arthroplasty (TJA) [1], traumatic brain injury [17], or spinal cord injury [4,33,55,61]. The incidence rate for HO varies from 15% to 90%, depending on the source of trauma and the grading criteria used [1,7,39,43,51].…”

Section: Introductionmentioning

confidence: 99%

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Shrivats

Hsu

Averick

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) may occur after musculoskeletal trauma, traumatic brain injury, and total joint arthroplasty. As such, HO is a compelling clinical concern in both military and civilian medicine. A possible etiology of HO involves dysregulated signals in the bone morphogenetic protein osteogenic cascade. Contemporary treatment options for HO (ie, nonsteroidal antiinflammatory drugs and radiation therapy) have adverse effects associated with their use and are not biologically engineered to abrogate the molecular mechanisms that govern osteogenic differentiation. Questions/purposes We hypothesized that (1) nanogelmediated short interfering RNA (siRNA) delivery against Runt-related transcription factor 2 (Runx2) and osterix (Osx) genes will decrease messenger RNA expression; (2) inhibit activity of the osteogenic marker alkaline phosphatase (ALP); and (3) inhibit hydroxyapatite (HA) deposition in osteoblast cell cultures. Methods Nanogel nanostructured polymers delivered siRNA in 48-hour treatment cycles against master osteogenic regulators, Runx2 and Osx, in murine calvarial preosteoblasts (MC3T3-E1.4) stimulated for osteogenic differentiation by recombinant human bone morphogenetic protein (rhBMP-2). The efficacy of RNA interference (RNAi) therapeutics was determined by quantitation of messenger RNA knockdown (by quantitative reverse transcription-polymerase chain reaction), downstream protein knockdown (determined ALP enzymatic activity assay), and HA deposition (determined by OsteoImage TM assay). Results Gene expression assays demonstrated that nanogelbased RNAi treatments at 1:1 and 5:1 nanogel:short interfering RNA weight ratios reduced Runx2 expression by 48.59% ± 19.53% (p \ 0.001) and 43.22% ± 18.01% (both p \ 0.001). The same 1:1 and 5:1 treatments against both Runx2 and Osx reduced expression of Osx by 51.65% ± 10.85% and 47.65% ± 9.80% (both p \ 0.001). Moreover, repeated 48-hour RNAi treatment cycles against Runx2 and Osx rhBMP-2 administration reduced ALP activity after 4 and 7 days. ALP reductions after 4 days in culture by nanogel 5:1 and 10:1 RNAi treatments were 32.4% ± 12.0% and 33.6% ± 13.8% (both p \ 0.001). After 7 days in culture, nanogel 1:1 and 5:1 RNAi treatments produced 35.9% ± 14.0% and 47.7% ± 3.2% reductions in ALP activity. Osteoblast mineralization data after 21 days suggested that Two of the authors (ARS, EH) contributed equally.

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Picture of the Month—Diagnosis

2008

Arch Pediatr Adolesc Med

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Heterotopic Ossification

Cited by 310 publications

References 33 publications

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Osteogenic Gene Expression Correlates With Development of Heterotopic Ossification in War Wounds

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Picture of the Month—Diagnosis

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