title: Multiple roles of the SO4(2-)/Cl-/OH- exchanger protein Slc26a2 in chondrocyte functions.
abstract: Mutations in the SO4(2-)/Cl(-)/OH(-) exchanger Slc26a2 cause the disease diastrophic dysplasia (DTD), resulting in aberrant bone development and, therefore, skeletal deformities. DTD is commonly attributed to a lack of chondrocyte SO4(2-) uptake and proteoglycan sulfation. However, the skeletal phenotype of patients with DTD is typified by reduction in cartilage and osteoporosis of the long bones. Chondrocytes of patients with DTD are irregular in size and have a reduced capacity for proliferation and terminal differentiation. This raises the possibility of additional roles for Slc26a2 in chondrocyte function. Here, we examined the roles of Slc26a2 in chondrocyte biology using two distinct systems: mouse progenitor mesenchymal cells differentiated to chondrocytes and freshly isolated mouse articular chondrocytes differentiated into hypertrophic chondrocytes. Slc26a2 expression was manipulated acutely by delivery of Slc26a2 or shSlc26a2 with lentiviral vectors. We demonstrate that slc26a2 is essential for chondrocyte proliferation and differentiation and for proteoglycan synthesis. Slc26a2 also regulates the terminal stage of chondrocyte cell size expansion. These findings reveal multiple roles for Slc26a2 in chondrocyte biology and emphasize the importance of Slc26a2-mediated protein sulfation in cell signaling, which may account for the complex phenotype of DTD.
authors.affiliation: From the Department of Biological Science, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Meeyoung
authors.initials: M
authors.lastname: Park
authors.forename: Ehud
authors.initials: E
authors.lastname: Ohana
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000838:Anions / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D000838:Anions; D011509:Proteoglycans; C513264:Slc26a2 protein, mouse; D000076988:Sulfate Transporters
keywords: Anion Transport; Cellular Regulation; Chondrocytes; Insulin-like Growth Factor (IGF); Transporters