Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)

Shore, Eileen M.; Kaplan, Frederick S.

doi:10.1016/j.bone.2008.05.013

Cited by 113 publications

(104 citation statements)

References 72 publications

(89 reference statements)

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“…Perhaps the most extreme cases of ectopic ossification can be found in patients with FOP [21], which is induced by a combination of genetic mutations and acute inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic lineage commitment of mesenchymal stem cells from patients with ossification of the posterior longitudinal ligament

Harada

Furukawa

Asari

et al. 2014

Biochemical and Biophysical Research Communications

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Ectopic bone formation is thought to be responsible for ossification of the posterior longitudinal ligament of the spine (OPLL). Mesenchymal stem cells (MSCs) were isolated from spinal ligaments and shown to play a key role in the process of ectopic ossification. The purpose of this study was to explore the capacity of these MSCs to undergo lineage commitment and to assess the gene expression changes between these committed and uncommitted MSCs between OPLL and non-OPLL patients. Spinal ligament-derived cells were obtained from OPLL patients or patients with cervical spondylotic myelopathy (non-ossified) for comparison (n=8 in each group). MSCs from the two patient cohorts were evaluated for changes in colony forming ability; osteogenic, adipogenic and chondrogenic differentiation potential; and changes in gene expression following induction with lineage-specific conditions. We show that the osteogenic differentiation potential was significantly higher in MSCs from OPLL patients than in those from non-OPLL patients. In addition, alkaline phosphatase activity and several osteogenic-related genes expressions (bone morphogenetic protein 2, runt-related transcription factor 2 and alkaline phosphatase) were significantly higher in the OPLL group than in the non-OPLL group. However, single cell cloning efficiency, adipogenic and chondrogenic differentiation, and the expression of adipogenic and 2 chondrogenic-related genes were equivalent between MSCs harvested from OPLL and non-OPLL patient samples. These findings suggest an increase in the osteogenic differentiation potential of MSCs from OPLL patients and that this propensity toward the osteogenic lineage may be a causal factor in the ossification in these ligaments.

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“…Perhaps the most extreme cases of ectopic ossification can be found in patients with FOP [21], which is induced by a combination of genetic mutations and acute inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic lineage commitment of mesenchymal stem cells from patients with ossification of the posterior longitudinal ligament

Harada

Furukawa

Asari

et al. 2014

Biochemical and Biophysical Research Communications

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“…This is much like the circumstances in patients with FOP where constitutive BMP signaling sensitizes muscle to mild trauma. 21,22 The cellular source of HO remains undefined. Previous studies have suggested that endothelial progenitors may be the responsible for the development of HO and BMP signaling plays a critical role in promoting endothelial-mesenchymal transition.…”

Section: Discussionmentioning

confidence: 99%

“…A mouse model of fibrodysplasia ossificans progressive (FOP), however, has proven to be a particularly valuable tool to study traumatic HO because of its trauma inducible nature. [19][20][21][22] In this model an activating mutation in ACVR1/ALK2, a type-I BMP receptor sensitizes the muscle to injury-induced HO. Other trauma-associated models include the use of BMPs in combination with cardiotoxin (CTX) or physical damage induced by crushing the muscle with surgical tweezers.…”

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confidence: 99%

A novel mouse model of trauma induced heterotopic ossification

Liu

Kang

Shahnazari

et al. 2013

Journal Orthopaedic Research

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Severe soft tissue trauma is associated with heterotopic ossification (HO), the abnormal deposition of bone at extraskeletal sites. The pathophysiology of the development of trauma-induced HO remains largely unknown due in part to the lack of appropriate animal models. In this study, we sought to develop a new trauma-induced HO mouse model using muscle impact injury combined with low dose BMP-2. BMP-2 at doses ranging from 0 to 2 mg was injected into quadriceps muscles of adult male C57/BL6 mice. Animals then received a one-time quadriceps impaction injury to mimic the trauma associated with severe injuries. HO was monitored using in vivo microCT scanning at 1, 2, 4, and 8 weeks after treatment. After trauma, the expression of BMP-2, -4, BMP receptor 1, SOX9 and RUNX2 were increased in muscle. Although little or no HO was observed in mice receiving 1 mg BMP-2, combining this dose with muscle trauma produced an abundance of HO. At higher doses of BMP-2, trauma did not augment mineral deposition. These results suggest that BMP-2 signaling can sensitize muscle to trauma-induced HO. They also provide the basis for a new model to study the pathogenesis of trauma-induced HO. ß

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“…4) The mean age at the appearance of the first lesion is three years and eleven months. 1) In this case, no specific clinical examination was performed even though the anomaly of his great toes was found when the patient was only four years old.…”

Section: Discussionmentioning

confidence: 99%

“…4) Early FOP lesions contain an intense perivascular B-cell and Tcell lymphocytic infiltration. Subsequent migration of mononuclear inflammatory cells into affected muscle precedes widespread myonecrosis.…”

Section: Discussionmentioning

confidence: 99%

Surgical Treatment Combined with NSAIDs in Fibrodysplasia Ossificans Progressiva

Seok

Cho

Lee

2012

ATCS

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Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification. There is no effective treatment. Conservative management is unsuccessful, and operation result in failure because new ectopic bone forms at the operative site. We report a 10-year-old boy with FOP who underwent surgical management combined with non-steroidal anti-inflammatory drugs (NSAIDs).Keywords: ectopic ossification, fibrodysplasia ossificans progressiva, chest wall Ann Thorac Cardiovasc Surg 2012; 18: 61-63 doi: 10.5761/atcs.cr.11.01677 larged. It was hard, 6-cm sized, and palpated over the right pectoralis muscle. He complained of a progressively decreased range of motion in his right shoulder due to pain (45° of forward elevation, and 45° of abduction). Physical examination revealed typical congenital malformations of the great toes (Fig. 1). His parents did not show any similar abnormalities during their physical examinations. No history of local trauma was reported. A chest roentgenogram demonstrated an abnormal calcification. A computed tomography scan showed a 6-cm sized abnormal heterotopic ossification between the pectoralis major muscle and pectoralis minor muscle (Fig. 2). The diagnosis of FOP was made based on the typical features including congenital malformations of great toes and progressive heterotopic ossification. Surgical excision of heterotopic ossification from the right chest was performed to improve range of motion for supportive therapy. The intubation was difficult owing to stiffness of the neck during the preoperative induction. The heterotopic bone located in the anterior aspect of his chest was excised as much as possible via anterior approach. We incised pectoralis major muscle and length of incision was about 5cm. During the operation, meticulously cautious efforts were made to avoid surgical trauma. An operation site incision and blunt muscular dissection was applied as little as possible. Convalescence was uneventful. On the second postoperative day, the patient started active physiotherapy. Naproxen (500 mg, once daily, orally) was administered for two weeks

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Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)

Cited by 113 publications

References 72 publications

Osteogenic lineage commitment of mesenchymal stem cells from patients with ossification of the posterior longitudinal ligament

Osteogenic lineage commitment of mesenchymal stem cells from patients with ossification of the posterior longitudinal ligament

A novel mouse model of trauma induced heterotopic ossification

Surgical Treatment Combined with NSAIDs in Fibrodysplasia Ossificans Progressiva

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