A review of the biomarkers and in vivo models for the diagnosis and treatment of heterotopic ossification following blast and trauma-induced injuries

Kazezian, Zepur; Bull, Anthony M.J.

doi:10.1016/j.bone.2020.115765

Cited by 17 publications

(10 citation statements)

References 105 publications

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“…Although there have been reports of HO in many tissues ( Lees-Shepard and Goldhamer, 2018 ), there have been no reports of calcification being replaced by HO. Acquired musculoskeletal trauma-induced HO and neurogenic trauma-induced HO are caused by a mixture of intrachondral and intramembranous ossification ( Kazezian and Bull, 2021 ). Non-traumatic HO was found on the wrists of dialysis patients, with elevated blood levels of PTH and BAP, and frequent wrist movements have been reported to induce microtrauma to calcification and bone formation ( Hatano et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Cancellous bone-like tissue replacement from calcinosis in patients with systemic sclerosis with multiple external root resorption

et al. 2022

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Calcinosis is frequently observed in patients with systemic sclerosis (SSc). The fundamental treatment of calcinosis has not yet been established. During follow-up, calcinosis in the subcutaneous surface is often spontaneously extracted or remains confined by fibrous tissues. We previously identified a new symptom in SSc patients, multiple external root resorption (MERR), and these patients had calcifications in the nasal spine. Here, we report for the first time that calcinosis at the nasal spine in patients with MERR can be replaced by cancellous bone-like tissue. Patients 1 and 2 were a 62-year-old Japanese female and a 45-year-old Japanese female (respectively) with MERR who had been previously treated for SSc (Patient 1: limited type, positive for anti-centromere antibody; Patient 2: diffuse type, positive for anti-Scl70 and anti-SS-A antibodies). Patient 3 was a 57-year-old female with MERR who had been previously treated for SSc (diffuse type, positive anti-Scl-70 antibody) and underwent denosumab injection for osteoporosis. Cone-beam computed tomography (CBCT) and CT images in the calcifications at the nasal spine in Patient 1 and 2 were replaced with cancellous bone-like tissue, but not in Patient 3. Serum laboratory examination was performed to assess the systemic bone disease. All three patients had normal clinical data within the references, apart from slightly higher 1,25-dihydroxyvitamin D levels in Patient 1. SSc patients with calcinosis in the maxillofacial area need to be examined carefully for bone replacement using CBCT or CT.

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Section: Discussionmentioning

confidence: 99%

Cancellous bone-like tissue replacement from calcinosis in patients with systemic sclerosis with multiple external root resorption

et al. 2022

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“…However, there are several complications such as hemorrhage and the recurrence rate of HO after surgery is relatively high (5,6). Trauma during the surgery may also increase the size of recurrent lesions and induce more ectopic calcification (18).…”

Section: Discussionmentioning

confidence: 99%

“…Non-steroidal anti-inflammatory drugs, radiation therapy, or a combination of the two, have been used to manage inflammation and chronic pain with limited success for prophylaxis of HO (5,6).…”

Section: Introductionmentioning

confidence: 99%

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Engineered Myeloid Precursors Differentiate into Osteoclasts and Resorb Heterotopic Ossification in Mice

Rementer

Yavirach

Buranaphatthana

et al. 2022

Preprint

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Heterotopic ossification (HO) is prevalent following orthopedic trauma, traumatic brain and spinal cord injuries, brain, and limb amputations, particularly in combat veterans. HO causes pain, limited mobility and decreased quality of life. Current treatments are limited and have significant complications with high recurrence rates, underscoring the need for improved therapeutic interventions. In this study, we used genetically engineered osteoclasts (OCs) as a cell therapy to treat HO. Inducible, engineered myeloid precursors (iRANK cells) treated with chemical inducer of dimerization (CID) differentiated into TRAP+ multinucleated OCs, expressed functional osteopontin, and resorbed mineralized tissues in vitro. To investigate if iRANK OCs could reduce HO in vivo, HO lesions were induced by injections of BMP-2, and iRANK cells were locally delivered to ectopic bone nodules with concomitant systemic administration of CID. Micro-CT and histology showed that HO lesions were significantly reduced, and more OCs were observed in the cell-treated group compared to the control. Moreover, many OCs were TRAP, MMP9, and GFP-positive indicating that they differentiated from delivered iRANK cells. Thus, our data confirm the ability of engineered myeloid precursors to differentiate into OCs and resorb HO lesions in vivo paving the way for OC delivery as a promising approach for HO treatment.

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“…Multiple lines of evidence suggest that the in ammatory response is closely associated with heterotopic ossi cation [8][9][10]. Undoubtedly, the process is extremely complex and the in ammatory state regulated by the involvement of various in ammatory factors will directly affect the osteogenic process [11,12].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17A promotes proliferation and osteogenic differentiation of human ligamentum flavum cells through regulation of β-catenin nuclear translocation

Lin

Jiang

Xiang

et al. 2022

Preprint

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Thoracic ossification of the ligamentum flavum (TOLF) is the leading cause of thoracic spinal stenosis with no specifc treatment available. IL-17A has received widespread attention for its key contribution in the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF. Our results showed that IL-17A expression was elevated in ossified ligamentum flavum tissue compared to normal ligamentum flavum. In in vitro experiments, IL-17A stimulation promoted the proliferation and osteogenic differentiation of ligamentum flavum cells (LFCs) derived from TOLF patients. Mechanistically, we found that IL-17A stimulation promoted nuclear translocation of β-catenin, whereas silencing of β-catenin attenuated IL-17A-induced proliferation and osteogenic differentiation of LFCs. Furthermore, co-culture of T helper 17 (Th17) cells with LFCs showed that IL-17A secreted by Th17 cells significantly enhanced the accumulation of β-catenin in the nucleus, as well as the proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A. Our study demonstrates that IL-17A secreted by Th17 cells in the lesion microenvironment may be involved in TOLF by regulating nuclear translocation of β-catenin to promote proliferation and osteogenic differentiation of LFCs. This study helps to elucidate the pathological mechanism of TOLF and suggests the possibility of IL-17A as a potential target for the prevention and treatment of TOLF.

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A review of the biomarkers and in vivo models for the diagnosis and treatment of heterotopic ossification following blast and trauma-induced injuries

Cited by 17 publications

References 105 publications

Cancellous bone-like tissue replacement from calcinosis in patients with systemic sclerosis with multiple external root resorption

Cancellous bone-like tissue replacement from calcinosis in patients with systemic sclerosis with multiple external root resorption

Engineered Myeloid Precursors Differentiate into Osteoclasts and Resorb Heterotopic Ossification in Mice

Interleukin-17A promotes proliferation and osteogenic differentiation of human ligamentum flavum cells through regulation of β-catenin nuclear translocation

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