The Fibrodysplasia Ossificans Progressiva Lesion

Identification of Progenitor Cells That Contribute to Heterotopic Skeletogenesis

“…3, A and B). Histopathological evaluation at different time points revealed that the major sequential pathological changes in heterotopic ossification in cardiotoxin-injected Nse-BMP4 mice were essentially identical to those observed in fibrodysplasia ossificans progressiva lesions or in experimental lesions following local injection of BMP4 into mouse skeletal muscle 10,31 . In all cases, we saw an intense perivascular mononuclear cell infiltrate consisting of macrophages and lymphocytes, muscle degeneration, and an intense fibroproliferative response, followed by robust chondrogenesis and finally osteogenesis with heterotopic marrow elements (Fig.…”

Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements

“…Data of our case series confirm great variability in severity of the disease, including differences in age of onset, flare-up inducing stimuli, frequency and duration of flare-ups, rate of progression and different consequences on the quality of life of affected people, with some reaching a more severe degree of disability very early in childhood and others later in adulthood, as already reported. 3,4,35 Interestingly, studies of monozygotic twins with FOP, all of them presenting with congenital toe malformations, but displaying variability in clinical phenotype evolution, suggest that environmental factors also can affect the phenotypic variability. 36 Our findings add relevant information that contributes to identify the molecular and cellular mechanisms that cause FOP and for developing targets for therapeutic intervention.…”

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

“…Heterotopic bone formation is episodic with ossification sites generally forming in predictable temporal and spatial patterns, with the first episodes typically occurring along the upper back and neck [9,15,18]. However, the natural progression of the disease can be altered by environmental factors, such as soft tissue injury.…”

“…FOP heterotopic bone characteristically forms through an endochondral pathway [18,24]. We have recognized several stages of FOP lesion formation leading to mature FOP heterotopic bone: lymphocytic infiltration (inflammation), degradation of muscle tissue, fibroproliferative and highly angiogenic stages, cartilage and finally bone [25,26].…”