Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2.
We have examined the effects of BMP-2 on the expression of bone matrix proteins in both human bone marrow stromal cells (HBMSC) and human osteoblasts (HOB) and their proliferation and mineralization. Both HBMSC and HOB express BMP-2/-4 type I and type II receptors. Treatment of these two cell types with BMP-2 for 4 weeks in the presence of beta-glycerophosphate and ascorbic acid results in mineralization of their matrix. BMP-2 increases the mRNA level and activities of alkaline phosphatase and elevates the mRNA levels and protein synthesis of osteopontin, bone sialoprotein, osteocalcin, and alpha 1(I) collagen in both cell types. Whereas the mRNA level of decorin is increased, the mRNA concentration of biglycan is not altered by BMP-2. No effect on osteonectin is observed. The effect of BMP-2 on bone matrix protein expression is dose dependent from 25 to 100 ng/ml and is evident after 1-7 days treatment. In the presence of BMP-2, proliferation of HBMSC and HOB is decreased under either serum-free condition or in the presence of serum. Thus, BMP-2 has profound effects on the proliferation, expression of most of the bone matrix proteins and the mineralization of both relatively immature human bone marrow stromal preosteoblasts and mature human osteoblasts.
Lecanda
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Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Avioli
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Cheng
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001857:Bone Matrix / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics; D053495:Osteopontin; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D017978:Receptors, Growth Factor; D012795:Sialoglycoproteins / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D011509:Proteoglycans; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D053495:Osteopontin; D003094:Collagen; D052004:Bone Morphogenetic Protein Receptors; D000469:Alkaline Phosphatase