title: The role of connective tissue growth factor (CTGF/CCN2) in skeletogenesis.
abstract: Connective tissue growth factor (CTGF) is a 38 kDa, cysteine rich, extracellular matrix protein composed of 4 domains or modules. CTGF has been shown to regulate a diverse array of cellular functions and has been implicated in more complex biological processes such as angiogenesis, chondrogenesis, and osteogenesis. A role for CTGF in the development and maintenance of skeletal tissues first came to light in studies demonstrating its expression in cartilage and bone cells, which was dramatically increased during skeletal repair or regeneration. The physiological significance of CTGF in skeletogenesis was confirmed in CTGF-null mice, which exhibited multiple skeletal dysmorphisms as a result of impaired growth plate chondrogenesis, angiogenesis, and bone formation/mineralization. Given the emerging importance of CTGF in osteogenesis and chondrogenesis, this review will focus on its expression in skeletal tissues, its effects on osteoblast and chondrocyte differentiation and function, and the skeletal implications of ablation or over-expression of CTGF in knockout or transgenic mouse models, respectively. In addition, this review will examine the role of integrin-mediated signaling and the regulation of CTGF expression as it relates to skeletogenesis. We will emphasize CTGF studies in bone or bone cells, and will identify opportunities for future investigations concerning CTGF and chondrogenesis/osteogenesis.
authors.affiliation: Basic Sciences Department, The Commonwealth Medical College, Scranton, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Arnott
authors.forename: Alex G
authors.initials: AG
authors.lastname: Lambi
authors.forename: Christina
authors.initials: C
authors.lastname: Mundy
authors.forename: Honey
authors.initials: H
authors.lastname: Hendesi
authors.forename: Robin A
authors.initials: RA
authors.lastname: Pixley
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Owen
authors.forename: Fayez F
authors.initials: FF
authors.lastname: Safadi
authors.forename: Steven N
authors.initials: SN
authors.lastname: Popoff
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000502:physiology*; D000077542:Eptifibatide; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D010455:Peptides / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D000077542:Eptifibatide