2013/12/04 by Meeyoung Park, Ehud Ohana, Soo Young Choi +3 · 1 citation
Environmental Science · Medicine · Biochemistry, Genetics and Molecular Biology · Chemistry · #Physiological and biochemical adaptations #Osteoarthritis Treatment and Mechanisms #Cancer, Hypoxia, and Metabolism #Chondrocyte #Cartilage #Cell biology #Mesenchymal stem cell #Progenitor cell #Proteoglycan #Cellular differentiation #Phenotype #Biology #Endochondral ossification #Chemistry #Stem cell #Anatomy #Biochemistry #Gene
paper · pdf · doi:10.1074/jbc.m113.503466
openalex publication_date 2013/12/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
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.