Extracellular Matrix and Developing Growth Plate
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Growth plate is a specialized cartilaginous structure that mediates the longitudinal growth of skeletal bones. It consists of ordered zones of chondrocytes that secrete an extracellular matrix (ECM) composed of specific types of collagens and proteoglycans. Several heritable human skeletal dysplasias are caused by mutations in these ECM components and this review focuses on the roles of type II, IX, X, and XI collagens, aggrecan, matrilins, perlecan, and cartilage oligomeric matrix protein in the growth plate as deduced from human disease phenotypes and mouse models. Substantial advances have been achieved in deciphering the interaction networks and individual roles of these components in the construction of the growth plate ECM. Furthermore, ER stress and other cellular responses have been identified as key downstream effects of the ECM mutations contributing to abnormal growth plate development. The next challenge is to utilize the molecular level knowledge for the development of potential therapeutics.
KeywordsGrowth plate Extracellular matrix Collagen Aggrecan Matrilin Perlecan Cartilage oligomeric matrix protein ER stress
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Conflict of Interest
J. Myllyharju has received research grants from FibroGen Inc.
Human and Animal Rights and Informed Consent
All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.
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