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Bone 2019 Mar 8. Epub 2019 Mar 8.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Internal Medicine Section Endocrinology, Amsterdam Bone Center, Amsterdam Movement Sciences, the Netherlands. Electronic address:

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Read More

Dev Dyn 2019 Mar 10. Epub 2019 Mar 10.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT) / Charité Virchow Campus, Berlin, Germany.

Background: This study analyzes Prx1-specific conditional knockout of Acvr1 aiming to elucidate the endogenous role of Acvr1 during limb formation in early embryonic development. ACVR1 can exhibit activating and inhibiting function in BMP signaling. ACVR1 gain-of-function mutations can cause the rare disease Fibrodysplasia Ossificans Progressiva (FOP), where patients develop ectopic bone replacing soft tissue, tendons and ligaments. Read More

J Musculoskelet Neuronal Interact 2019 Mar;19(1):118-122

3rd Paediatric Dept, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.

Myossitis ossificans (MO) is a benign disorder characterized by heterotopic bone formation in skeletal muscle. It is divided in three types, fibrodysplasia ossificans progressive (FOP), myositis ossificans circumscripta or traumatica (MOT) and myositis ossificans without a history of trauma (non traumatic or pseudomalignant MO). Myositis ossificans is extremely rare in children younger than 10 years. Read More

Chem Pharm Bull (Tokyo) 2019 ;67(3):224-235

Drug Discovery Chemistry Platform Unit, RIKEN Center for Sustainable Resource Science.

Mutant activin receptor-like kinase-2 (ALK2) was reported to be closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG), and therefore presents an attractive target for therapeutic intervention. Through in silico virtual screenings and structure-activity relationship studies assisted by X-ray crystallographic analyses, a novel series of bis-heteroaryl pyrazole was identified as potent inhibitors of ALK2 (R206H). Derived from in silico hit compound RK-59638 (6a), compound 18p was identified as a potent inhibitor of ALK2 (R206H) with good aqueous solubility, liver microsomal stability, and oral bioavailability. Read More

Stem Cells 2019 Feb 20. Epub 2019 Feb 20.

Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Read More

J Orthop Case Rep 2018 Sep-Oct;8(5):36-39

Department of Medical Genetics, Istanbul University, Istanbul School of Medicine, Sehremini, Fatih, Istanbul, Turkey.

Introduction: Fibrodysplasia ossificans progressiva previously known as myositis ossificans progressiva is a rare connective tissue disorder with autosomal dominant genetic inheritance. Patients develop heterotrophic ossification starting with the first decade of life. Diagnosis is extremely difficult until ossifications are visible. Read More

Elife 2019 Jan 30;8. Epub 2019 Jan 30.

Department of Molecular and Cell Biology, University of Connecticut, Storrs, United States.

We respond to concerns expressed by Pacifici and Shore (2019) about a recent paper (Lees-Shepard and Goldhamer, 2018a) in which we reported that the drug palovarotene can have severe side effects in a mouse model of fibrodysplasia ossificans progressiva. Read More

Stem Cell Res Ther 2019 Jan 11;10(1):14. Epub 2019 Jan 11.

School of Basic Medical Sciences, Anhui Medical University, 81 Meishan road, Hefei, 230032, China.

Background: Heterotopic ossification (HO), either acquired (aHO) or hereditary, such as fibrodysplasia ossificans progressiva (FOP), is a serious condition without effective treatment. Understanding of the core process of injury-induced HO is still severely limited.

Methods: Double-pulse thymidine analog labeling was used to explore the distinctive domains evolved in injury-induced lesions in an animal model of HO (Nse-BMP4). Read More

Ethiop J Health Sci 2018 Jul;28(4):513-516

Department of Pediatrics and Child Health, School of Medicine, College of Health Sciences, Addis Ababa University, Ethiopia.

Background: Fibrodysplasia ossificans progressiva (FOP), also known as Myositis ossificans progressiva or Munchmeyer's disease, is an extremely rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO). The disease is characterized by congenital skeletal anomalies and progressive ectopic bone formation in connective tissues such as ligaments, muscles and tendons. The disease has an incidence of about 1 in 2 million population. Read More

Laryngoscope 2018 Dec 23. Epub 2018 Dec 23.

Division of Otolaryngology-Head and Neck Surgery, Seattle Children's Hospital, Seattle, Washington, U.S.A.

Fibrodysplasia ossificans progressiva (FOP) is a rare disorder that causes heterotopic bone formation leading to chest wall and spinal deformities. This case describes an 11-year-old female with FOP who presented in respiratory failure necessitating two emergent fiberoptic nasotracheal intubations. The patient had severe trismus, rotary flexion of the neck, and distortion of the airway. Read More

Br J Clin Pharmacol 2018 Nov 30. Epub 2018 Nov 30.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease in which heterotopic bone forms in muscle and soft tissue, leading to joint dysfunction and significant disability. FOP is progressive and many patients are wheelchair-bound by the 3rd decade of life. FOP is caused by an activating mutation in the ACVR1 gene, which encodes the activin A Type 1 receptor. Read More

JCI Insight 2018 Nov 15;3(22). Epub 2018 Nov 15.

Division of Endocrinology and Metabolism, Department of Medicine, and the Institute for Human Genetics, UCSF, San Francisco, California, USA.

Background: Inflammation helps regulate normal growth and tissue repair. Although bone morphogenetic proteins (BMPs) and inflammation are known contributors to abnormal bone formation, how these pathways interact in ossification remains unclear.

Methods: We examined this potential link in patients with fibrodysplasia ossificans progressiva (FOP), a genetic condition of progressive heterotopic ossification caused by activating mutations in the Activin A type I receptor (ACVR1/ALK2). Read More

Int J Mol Sci 2018 Nov 13;19(11). Epub 2018 Nov 13.

Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan.

Bone is a unique organ because it can be experimentally induced in soft tissues by implanting a single growth factor, bone morphogenetic protein (BMP). Heterotopic bone-inducing activity was found in demineralized bone matrix in 1965. The characterization of this activity in bone enabled the purification and molecular cloning of BMPs and showed that they are members of the transforming growth factor-β (TGF-β) superfamily. Read More

J Cell Physiol 2018 Nov 11. Epub 2018 Nov 11.

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.

Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by heterotopic ossification (HO). The disease is caused by a mutation in the activin receptor type 1 (ACVR1) gene that enhances this receptor's responsiveness to Activin-A. Binding of Activin-A to the mutated ACVR1 receptor induces osteogenic differentiation. Read More

Methods Mol Biol 2019 ;1891:247-255

Department of Orthopaedic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of progressive extra-skeletal ossification, is the most disabling form of heterotopic ossification (HO) in humans. Most people with FOP carry an activating mutation in a BMP type I receptor gene, ACVR1 , that promotes ectopic chondrogenesis and osteogenesis and in turn HO. Advances in elucidating the cellular and molecular events and mechanisms that lead to the ectopic bone formation are being made through the use of genetically engineered mouse models that recapitulate the human disease. Read More

Methods Mol Biol 2019 ;1891:155-163

Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.

Fibrodysplasia ossificans progressiva (FOP) is a rare human skeletal disease caused by constitutively activating mutations in the gene ACVR1, which encodes a type I BMP/TGFβ family member receptor. FOP is characterized by progressive heterotopic ossification (HO) of fibrous tissues, including skeletal muscle, tendons, and ligaments, as well as malformation of the big toes, vertebral fusions, and osteochondromas. Surgical interventions in patients often result in enhanced HO, which can exacerbate rather than improve diagnostic outcomes. Read More

Stem Cell Reports 2018 Nov 1;11(5):1106-1119. Epub 2018 Nov 1.

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disorder characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor gain-of-function mutations in ACVR1 (FOP-ACVR1), a type I receptor for bone morphogenetic proteins. Despite numerous studies, no drugs have been approved for FOP. Read More

Mol Biol Cell 2019 Jan 31;30(1):17-29. Epub 2018 Oct 31.

Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19104.

An activating bone morphogenetic proteins (BMP) type I receptor ACVR1 (ACVR1) mutation enhances BMP pathway signaling and causes the rare genetic disorder of heterotopic (extraskeletal) bone formation fibrodysplasia ossificans progressiva. Heterotopic ossification frequently occurs following injury as cells aberrantly differentiate during tissue repair. Biomechanical signals from the tissue microenvironment and cellular responses to these physical cues, such as stiffness and rigidity, are important determinants of cell differentiation and are modulated by BMP signaling. Read More

Rheumatol Int 2019 Mar 20;39(3):569-576. Epub 2018 Oct 20.

Department of Physical Medicine and Rehabilitation, Marmara University School of Medicine, 34899 Pendik Ust Kaynarca, Istanbul, Turkey.

Fibrodysplasia ossificans progressiva (FOP), is a rare autosomal dominant connective tissue disease with a prevalence of 1 in 2 million. It is characterized by congenital foot deformities and multiple heterotopic ossifications in fibrous tissue. It usually starts with painful soft tissue swellings occurring with attacks at the ages of three or four. Read More

Br J Clin Pharmacol 2018 Oct 3. Epub 2018 Oct 3.

Department of Internal Medicine section Endocrinology, Amsterdam Bone Center, Amsterdam University Medical Centers location VUmc, Amsterdam, the Netherlands.

Clinical trials for orphan diseases are critical for developing effective therapies. One such condition, fibrodysplasia ossificans progressiva (FOP; MIM#135100), is characterized by progressive heterotopic ossification (HO) that leads to severe disability. Individuals with FOP are extremely sensitive to even minor traumatic events. Read More

J Pathol 2019 Jan 27;247(1):9-20. Epub 2018 Nov 27.

Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.

Bone morphogenetic proteins (BMPs) are secreted cytokines that were initially discovered on the basis of their ability to induce bone. Several decades of research have now established that these proteins function in a large variety of physiopathological processes. There are about 15 BMP family members, which signal via three transmembrane type II receptors and four transmembrane type I receptors. Read More

Endocrinol Metab (Seoul) 2018 Sep;33(3):331-338

Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon. It is difficult to remove such heterotopic bones via internal medicine or invasive procedures. The identification of activin A receptor, type I gene mutations associated with FOP has allowed the genetic diagnosis of FOP. Read More

Elife 2018 09 18;7. Epub 2018 Sep 18.

Department of Molecular and Cell Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, United States.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by debilitating heterotopic ossification (HO). The retinoic acid receptor gamma agonist, palovarotene, and antibody-mediated activin A blockade have entered human clinical trials, but how these therapeutic modalities affect the behavior of pathogenic fibro/adipogenic progenitors (FAPs) is unclear. Using live-animal luminescence imaging, we show that transplanted pathogenic FAPs undergo rapid initial expansion, with peak number strongly correlating with HO severity. Read More

Cureus 2018 Jul 10;10(7):e2955. Epub 2018 Jul 10.

Department of Orthopaedics, All India Institute of Medical Sciences, Bhopal, IND.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by widespread areas of abnormal bone formation in muscles, ligaments, tendons and joint capsules. Typically, the symptoms begin in the first decade of life with episodes of painful inflammatory soft tissue swellings. Gradually, there occurs restriction of motion at various joints, severely limiting the activities of daily living and the quality of life of such patients by the third decade of life. Read More

Zebrafish 2018 12 5;15(6):536-545. Epub 2018 Sep 5.

1 Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine , Boston, Massachusetts.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant genetic disorder in humans characterized by the gradual ossification of fibrous tissues, including skeletal muscle, tendons, and ligaments. In humans, mutations in the Type I BMP/TGFβ family member receptor gene, ACVR1, are associated with FOP. Zebrafish acvr1l, previously known as alk8, is the functional ortholog of human ACVR1. Read More

Methods Mol Biol 2018 ;1828:497-502

Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive heterotopic ossification. More than 95% of cases are caused by a recurrent mutation (617G>A; R206H) of ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Recent studies revealed that ACVR1 induces heterotopic ossification by aberrant activation in response to activin A. Read More

Methods Mol Biol 2018 ;1828:31-55

Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada.

Exon skipping is a therapeutic approach that is feasible for various genetic diseases and has been studied and developed for over two decades. This approach uses antisense oligonucleotides (AON) to modify the splicing of pre-mRNA to correct the mutation responsible for a disease, or to suppress a particular gene expression, as in allergic diseases. Antisense-mediated exon skipping is most extensively studied in Duchenne muscular dystrophy (DMD) and has developed from in vitro proof-of-concept studies to clinical trials targeting various single exons such as exon 45 (casimersen), exon 53 (NS-065/NCNP-01, golodirsen), and exon 51 (eteplirsen). Read More

J Mol Model 2018 Aug 29;24(9):262. Epub 2018 Aug 29.

Department of Chemistry, Aligarh Muslim University, Aligarh, U.P., 202002, India.

Bone morphogenetic proteins (BMPs) are a family of more than 30 ligands and several receptors, such as activin like kinases (ALKs) and bone morphogenetic protein receptor (BMPR). Physiological significance of these proteins lies in their prominent role during homeostasis, apoptosis, tissue remodeling, embryonic patterning, and normal development. Fibrodysplasia ossificans progressive (FOP) is one among several other diseases caused by impaired BMP signaling. Read More

Development 2018 08 23;145(16). Epub 2018 Aug 23.

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan

Somites (SMs) comprise a transient stem cell population that gives rise to multiple cell types, including dermatome (D), myotome (MYO), sclerotome (SCL) and syndetome (SYN) cells. Although several groups have reported induction protocols for MYO and SCL from pluripotent stem cells, no studies have demonstrated the induction of SYN and D from SMs. Here, we report systematic induction of these cells from human induced pluripotent stem cells (iPSCs) under chemically defined conditions. Read More

Acta Reumatol Port 2018 Apr-Jun;43(2):156-158

All India Institute of Medical Sciences, New Delhi, India.

Fibrodysplasia ossificans progressiva is characterized by congenital skeletal anomalies and progressive heterotopic ossification. We present a 4 year old male patient who underwent unnecessary harmful multiple biopsies before the diagnosis of fibrodysplasia ossificans progressiva is made. Though rare, diagnosis of fibrodysplasia ossificans progressiva should be considered whenever characteristic radiographic features of multifocal heterotopic bone formation is seen along with the valgus deformities of the big toes. Read More

J Clin Anesth 2018 12 21;51:8-9. Epub 2018 Jul 21.

Department of Anesthesiology and Pain Medicine, Seattle Children's Hospital, University of Washington, United States of America. Electronic address:

J Nepal Health Res Counc 2018 Jul 4;16(2):245-247. Epub 2018 Jul 4.

Department of Oral Pathology, KIST Medical College and Teaching Hospital, Imadole, Lalitpur, Nepal.

Fibrodysplasia ossificans progressiva is a genetic disorder of the connective tissue differentiation characterized by congenital malformation of the big toes and progressive heterotopic ossification in the extra skeletal tissues like tendons, ligaments, fascia and skeletal muscles leading to permanent disability. The prevalence is one in two million people. During childhood, it may be asymptomatic but in later life, progressive stiffness of major joints renders movement of the individual impossible. Read More

J Orthop Case Rep 2018 Jan-Feb;8(1):39-43

Fellow in Pediatric Orthopedic Surgery Course, Hospital Regional de Alta Especialidad del Bajio, Leon, Guanajuato, Mexico.

Introduction: Fibrodysplasia ossificans progressiva (FOP) is the severest disease of ossification in the human. It forms an exoskeleton gradually. This process is started for a nodule that ossifies as days goes by. Read More

Br J Oral Maxillofac Surg 2018 06 3;56(5):427-429. Epub 2018 May 3.

Newcastle University, School of Dental Sciences, Framlington Place, Newcastle upon Tyne, NE2 4BW; Carlisle Dental Centre, Cumbria Partnership NHS Foundation Trust, Infirmary Street, Carlisle, CA2 7AN. Electronic address:

Fibrodysplasia ossificans progressiva is a rare genetic disease of connective tissue in which muscles, ligaments, and tendons ossify either spontaneously or after trauma. Patients can develop physical disabilities and restriction of respiratory function. A patient attended a maxillofacial surgery outpatient clinic with severe trismus and mouth opening limited to 2mm. Read More

Clin Nucl Med 2018 Jun;43(6):433-435

A 27-year-old woman had progressive bony ankylosis over both hands since she was 5 years old. Bony ankylosing over the peripheral joints and spine slowly progressed, and scoliosis surgery was performed at age 14. Recently, she developed difficulty walking, changing position, and opening her mouth. Read More

Bone 2018 07 5;112:71-89. Epub 2018 Apr 5.

Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, United States. Electronic address:

Heterotopic ossification (HO), the pathological extraskeletal formation of bone, can arise from blast injuries, severe burns, orthopedic procedures and gain-of-function mutations in a component of the bone morphogenetic protein (BMP) signaling pathway, the ACVR1/ALK2 receptor serine-threonine (protein) kinase, causative of Fibrodysplasia Ossificans Progressiva (FOP). All three ALKs (-2, -3, -6) that play roles in bone morphogenesis contribute to trauma-induced HO, hence are well-validated pharmacological targets. That said, development of inhibitors, typically competitors of ATP binding, is inherently difficult due to the conserved nature of the active site of the 500+ human protein kinases. Read More

Curr Opin Pharmacol 2018 06 31;40:51-58. Epub 2018 Mar 31.

Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address:

Heterotopic ossification (HO) involves the formation and accumulation of extraskeletal bone tissue at the expense of local tissues including muscles and connective tissues. There are common forms of HO that are triggered by extensive trauma, burns and other bodily insults, and there are also rare congenital severe forms of HO that occur in children with Fibrodysplasia Ossificans Progressiva or Progressive Osseous Heteroplasia. Given that HO is often preceded by inflammation, current treatments usually involve anti-inflammatory drugs alone or in combination with local irradiation, but are not very effective. Read More

Open Biol 2018 03;8(3)

Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan

Rapamycin inhibits TOR (target of rapamycin) kinase, and is being used clinically to treat various diseases ranging from cancers to fibrodysplasia ossificans progressiva. To understand rapamycin mechanisms of action more comprehensively, 1014 temperature-sensitive (ts) fission yeast () mutants were screened in order to isolate strains in which the ts phenotype was rescued by rapamycin. Rapamycin-rescued 45 strains, among which 12 genes responsible for temperature sensitivity were identified. Read More

Int J Mol Sci 2018 Mar 26;19(4). Epub 2018 Mar 26.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by progressive extra-skeletal ossification leading to cumulative and severe disability. FOP has an extremely variable and episodic course and can be induced by trauma, infections, iatrogenic harms, immunization or can occur in an unpredictable way, without any recognizable trigger. The causative gene is , encoding the Alk-2 type I receptor for bone morphogenetic proteins (BMPs). Read More

Bone 2018 04;109:1-2

Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104; Department of Genetics, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104; Department of The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104. Electronic address:

Bone 2018 06 15;111:101-108. Epub 2018 Mar 15.

Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Project of Clinical and Basic Research for FOP, Saitama Medical University, Saitama, Japan. Electronic address:

Various substitution mutations in ALK2, a transmembrane serine/threonine kinase receptor for bone morphogenetic proteins (BMPs), have been identified in patients with genetic disorders such as fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine glioma (DIPG) and heart defects. In this study, we characterized the ALK2 mutants R258G, G328V and F246Y, which were identified in patients with severe FOP, DIPG and unusual hereditary skeletal dysplasia, respectively. Both R258G and G328V were gain-of-function mutations, but F246Y was equivalent to wild-type ALK2. Read More

BMC Med Genet 2018 02 27;19(1):30. Epub 2018 Feb 27.

Department of Emergency Traumatic Surgery, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People's Republic of China.

Background: Fibrodysplasia ossificans progressiva (FOP), an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification, is caused by heterozygous activating mutations in activin A receptor, type I/activin-like kinase 2 (ACVR1/ALK2). The rarity of the disease makes it common to make a misdiagnosis and cause mismanagement.

Case Presentation: We reported a case of a sixteen-year-old male patient who had suffered from pain and swelling in the biopsy site for two months. Read More

Skeletal Radiol 2018 Aug 14;47(8):1043-1050. Epub 2018 Feb 14.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

Objective: Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by congenital skeletal deformities and soft tissue masses that progress to heterotopic ossification. Deformities of the great toes are distinctive, and heterotopic ossification in the soft tissues follows an expected anatomic and temporal pattern. In addition to heterotopic ossification, osteochondromata, middle ear ossification, demyelination, lymphedema, and venous thrombosis are characteristic. Read More

Nat Commun 2018 02 7;9(1):551. Epub 2018 Feb 7.

Department of Orthopedic Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.

Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by extraskeletal bone formation after injury. The exact pathogenesis of HO remains unknown. Here we show that TGF-β initiates and promotes HO in mice. Read More

Bone 2018 04 31;109:178-186. Epub 2018 Jan 31.

Department of Molecular & Cell Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT 06269, United States. Electronic address:

Put most simply, heterotopic ossification (HO) is the abnormal formation of bone at extraskeletal sites. HO can be classified into two main subtypes, genetic and acquired. Acquired HO is a common complication of major connective tissue injury, traumatic central nervous system injury, and surgical interventions, where it can cause significant pain and postoperative disability. Read More

Nat Commun 2018 02 2;9(1):471. Epub 2018 Feb 2.

Department of Molecular and Cell Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, 06269, USA.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that fibro/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in an accurate genetic mouse model of FOP (Acvr1 ). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients. Read More

Orphanet J Rare Dis 2018 01 22;13(1):18. Epub 2018 Jan 22.

Niemann-Pick UK, Suite 2, Vermont House, Concord, Washington, Tyne and Wear, NE37 2SQ, UK.

Background: Rare diseases are a global public health concern, affecting an estimated 350 million individuals. Only 5% of approximately 7000 known rare diseases have a treatment, and only about half have a patient advocacy organization. Biopharmaceutical companies face complex challenges in developing treatments for rare diseases. Read More

Bone 2018 04 7;109:56-60. Epub 2018 Jan 7.

Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:

Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late-adulthood, usually in the context of prior abdominal surgery. The mechanisms of MHO are unknown. Here we describe the case of a 72-year-old man with MHO. Read More

Bone 2018 04 4;109:225-231. Epub 2018 Jan 4.

Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

The large majority of cases of the autosomal dominant human disease fibrodysplasia ossificans progressiva (FOP) are caused by gain-of-function Arg206His mutations in the BMP type I receptor ACVR1 (ALK2). The Arg206His mutation is located in the GS domain of the type I receptor. This region is normally phosphorylated by the BMP type II receptor, which activates the type I receptor to phosphorylate its substrate, the signal transducer Smad1/5/8. Read More