Proteoglycans: key partners in bone cell biology.
The diversity of bone proteoglycan (PG) structure and localisation (pericellular, extracellular in the organic bone matrix) reflects a broad spectrum of biological functions within a unique tissue. PGs play important roles in organizing the bone extracellular matrix, taking part in the structuring of the tissue itself as active regulators of collagen fibrillogenesis. PGs also display selective patterns of reactivity with several constituents including cytokines and growth factors, such as transforming growth factor-beta or osteoprotegerin thereby modulating their bio-availability and biological activity in the bone tissue. In this review, the complex PG composition in bone will be addressed together with the specific role played by PGs (or their GAGs chains) in bone biology, as regulatory molecules for bone resorption and their involvement in bone tumor development. These roles have been determined after modulation of PG expression or mutations in their corresponding genes, which revealed specific roles for these compounds in bone pathologies (e.g. perlecan or glypican-3 mutations observed respectively in chondrodysplasia or dysmorphic syndrome). Finally, the potential therapeutic interest of PGs is discussed based on recent data, more particularly on bone tumor-associated osteolysis as these molecules are involved both in bone resorption and tumor development.
Lamoureux
François
F
EA3822-INSERM ERI7, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes cedex 1, France.
Baud'huin
Marc
M
Duplomb
Laurence
L
Heymann
Dominique
D
Rédini
Françoise
F
D000818:Animals; D001846:Bone Development / Q000235:genetics; D001859:Bone Neoplasms / Q000209:etiology / Q000628:therapy; D001862:Bone Resorption / Q000209:etiology / Q000235:genetics; D001842:Bone and Bones / Q000737:chemistry / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008954:Models, Biological; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D011509:Proteoglycans