Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in...

fibrodysplasia ossificans progressiva (fop) is a rare hereditary connective tissue disease characterized by the progressive ectopic ossification of ligaments, tendons, and facial and skeletal muscles throughout life. symptoms begin in childhood as localized soft tissue swellings. immobility and articular dysfunction appear with involvement of the spine and proximal extremities. the temporomandi...

Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification. Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase. POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidi...

Heterotopic ossification is a benign process of mature laminar bone formation in the soft tissues. A synonymous term used to describe this pathology in muscle is myositis ossificans. The pathogenesis is unclear, but is likely multifactorial. The basic pathology is thought to be ectopic production of osseous tissue as part of a repair process in response to tissue injury. This report describes a...

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 c...

In tetrapod long bones, Hedgehog signalling is required for osteoblast differentiation in the perichondrium. In this work we analyse skeletogenesis in zebrafish larvae treated with the Hedgehog signalling inhibitor cyclopamine. We show that cyclopamine treatment leads to the loss of perichondral ossification of two bones in the head. We find that the Hedgehog co-receptors patched1 and patched2 ...

Chondrocyte hypertrophy is essential for endochondral bone development. Unexpectedly, we discovered that MEF2C, a transcription factor that regulates muscle and cardiovascular development, controls bone development by activating the gene program for chondrocyte hypertrophy. Genetic deletion of Mef2c or expression of a dominant-negative MEF2C mutant in endochondral cartilage impairs hypertrophy,...

Heterotopic ossification (HO), deposition of para-articular ectopic bone, is associated with musculoskeletal trauma and certain congenital and metabolic disorders. Additionally, HO may follow paralysis from diverse traumatic and nontraumatic neurologic insults. We describe three cases of HO associated with catastrophic nontraumatic respiratory illness requiring prolonged chemical paralysis and ...