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Emerging evidence continues to support the functional importance of extracellular matrix (ECM) proteins in cellular signaling. In mineralizing tissues, including bone, cartilage, and vasculature, ECM proteins not only provide the microenvironment for propagation of crystal growth but also support and transmit mechanical cues to the cells, and these cues govern many aspects of cell function, including proliferation and differentiation. When cells interact with the matrix and produce their own matrix proteins, it is a form of intercellular communication. Although this “matricrine” signaling receives less research attention than chemical forms of intercellular communication, such as autocrine and paracrine signaling, it is important in biomineralization in both health and disease.
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In this issue of Circulation Research, Fu et al1 highlight the important role of the noncollagenous ECM protein, cartilage oligomeric matrix protein (COMP) in calcific atherosclerosis. COMP, a member of the thrombospondin-5 family of proteins, maintains cartilage structural integrity by binding collagen and other ECM proteins, such as aggrecan (chondroitin sulfate proteoglycan 1), aggregates of which give cartilage its springy resistance to compression.2–4 COMP overexpression enhances ECM organization and assembly by increasing total soluble glycosaminoglycan content and levels of aggrecan and collagen type II.5 Thus, COMP seems to control the assembly and maintenance of the tertiary architecture of ECM. Its homopentameric structure, like that of a spiny starfish, allows it to bind to multiple sites, bridging collagen fibrils to one another and bridging cells to matrix proteins and proteoglycans.6
ECM proteins interact with the intracellular cytoskeleton through mechanical links with integrins. As described elegantly by Ingber et al,7 as a tensegrity model, the mechanical features of ECM are central determinants of cell shape and, thus, cell behavior. One robust example of the ability of ECM mechanical …