title: Targeting the extracellular matrix: matricellular proteins regulate cell-extracellular matrix communication within distinct niches of the intervertebral disc.
abstract: The so-called "matricellular" proteins have recently emerged as important regulators of cell-extracellular matrix (ECM) interactions. These proteins modulate a variety of cell functions through a range of interactions with cell-surface receptors, hormones, proteases and structural components of the ECM. As such, matricellular proteins are crucial regulators of cell phenotype, and consequently tissue function. The distinct cell types and microenvironments that together form the IVD provide an excellent paradigm to study how matricellular proteins mediate communication within and between adjacent tissue types. In recent years, the role of several matricellular proteins in the intervertebral disc has been explored in vivo using mutant mouse models in which the expression of target matricellular proteins was deleted from either one or all compartments of the intervertebral disc. The current review outlines what is presently known about the roles of the matricellular proteins belonging to the CCN family, SPARC (Secreted Protein, Acidic, and Rich in Cysteine), and thrombospondin (TSP) 2 in regulating intervertebral disc cell-ECM interactions, ECM synthesis and disc tissue homeostasis using genetically modified mouse models. Furthermore, we provide a brief overview of recent preliminary studies of other matricellular proteins including, periostin (POSTN) and tenascin (TN). Each specific tissue type of the IVD contains a different matricellular protein signature, which varies based on the specific stage of development, maturity or disease. A growing body of direct genetic evidence links IVD development, maintenance and repair to the coordinate interaction of matricellular proteins within their respective niches and suggests that several of these signaling modulators hold promise in the development of diagnostics and/or therapeutics targeting intervertebral disc aging and/or degeneration.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Jake
authors.initials: J
authors.lastname: Bedore
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada; Department of Dentistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada. Electronic address: cheryle.seguin@schulich.uwo.ca.
authors.forename: Cheryle A
authors.initials: CA
authors.lastname: Séguin
mesh_terms: D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy*; D015676:Osteonectin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019063:Tenascin / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D000099262:Thrombospondin 2
chemical_list: D055511:CCN Intercellular Signaling Proteins; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D015676:Osteonectin; D019063:Tenascin; D019699:Thrombospondins; D000099262:Thrombospondin 2; C512835:POSTN protein, human; C577241:SPARC protein, human
keywords: Disc degeneration; Extracellular matrix; Intervertebral disc; Matricellular proteins; Microenvironment