1,25-Dihydroxyvitamin D3 inhibits synthesis and enhances degradation of proteoglycans in osteoblastic cells.
The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, on the metabolism of proteoglycans by an osteoblastic cell line MC3T3-E1 were studied. Cells metabolically labeled with [35S]sulfate and/or [3H]glucosamine synthesized large and small dermatan sulfate proteoglycans and heparan sulfate proteoglycan. The incorporation of [35S]sulfate into proteoglycans for 1 h was reduced by 1,25-(OH)2D3 in a dose-dependent manner with a maximum reduction of 40% obtained at 10(-8)M 1,25-(OH)2D3. This effect was observed for all the proteoglycans with the decrease for the large dermatan sulfate proteoglycan most prominent. Treatment with 1,25-(OH)2D3 did not influence the degree of sulfation nor the molecular size of the glycosaminoglycan chains. Thus, the change in the incorporation of [35S] sulfate reflects net change in the synthesis of proteoglycans. When cells were treated with beta-D-xyloside, 1,25-(OH)2D3 also inhibited net synthesis of dermatan sulfate glycosaminoglycan chains on this exogenous substrate suggesting that it decreases the capacity of the cells for glycosaminoglycan synthesis. The incorporation of [3H]glucosamine into hyaluronic acid was also inhibited up to 70% by 10(-8) M 1,25-(OH)2D3. Treatment with 24,25-dihydroxyvitamin D3 did not cause significant changes in the proteoglycan synthesis. Degradation of proteoglycans associated with the cell layer was enhanced by treatment with 1,25-(OH)2D3 at 10(-8) M. Proteoglycans exogenously added to the culture were also degraded with a cell-mediated process which was stimulated by treatment with 10(-8) M 1,25-(OH)2D3. These results demonstrate that 1,25-(OH)2D3 reduces the synthesis and stimulates the degradation of proteoglycans in osteoblastic cells in culture.
Takeuchi
Y
Y
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Matsumoto
T
T
Ogata
E
E
Shishiba
Y
Y
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism
D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D011508:Chondroitin Sulfate Proteoglycans; D003871:Dermatan Sulfate; D005944:Glucosamine; D006027:Glycosides; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D011509:Proteoglycans; D013431:Sulfates; C032649:dermatan sulfate proteoglycan; C010807:xylosides