Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis.
The principle function of articular cartilage is to provide a low friction load-bearing surface that facilitates free movement of joints. Maintenance of this surface depends on the maturational arrest of chondrocytes before terminal hypertrophic differentiation occurs [Exp. Cell Res. 216 (1995) 191; Osteoarthritis Cartilage 7 (1999) 389; J. Cell Biol. 139 (1997) 541; J. Cell Biol. 145 (1999) 783]. In contrast to endochondral ossification which involves a programmed process of chondrocyte maturation culminating in terminal hypertrophy and mineralization [Nat. Genet. 9 (1995) 15], articular chondrocytes (ACs) are constrained from completing the maturational program as evidenced by a lack of type X collagen (colX) and alkaline phosphatase expression [Arthritis Res. 3 (2001) 107; Biochem. J. 362 (2002) 473]. Also, ACs are not responsive to factors that impact the maturational process, including bone morphogenetic protein-2 (BMP-2), a potent stimulator of chondrocyte maturation [J. Orthop. Res. 14 (1996) 937]. Factors that constrain AC maturation are only relieved under unique circumstances such as in osteoarthritis (OA), where proliferation and an increase in the expression of hypertrophic hallmarks indicates that the cells have differentiated into a mature phenotype [Calcif. Tissue Int. 63 (2000) 230]. OA may thus involve the functional loss of mechanisms that arrest articular cartilage differentiation. Responsiveness to various growth or systemic factors translates into activation or repression of specific genes through transcriptional mediators. Understanding the downstream mechanisms involved in this process is of paramount importance. Thus, unraveling the molecular interplay between various factors that regulate chondrocyte maturation during OA occurrence and progression is the main focus of ongoing efforts.
Drissi
Hicham
H
The Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, United States. hicham_drissi@urmc.rochester.edu
Zuscik
Michael
M
Rosier
Randy
R
O'Keefe
Regis
R
D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D014157:Transcription Factors