Requirement of a bone morphogenetic protein for the maintenance and stimulation of osteoblast differentiation.
The requirement of a bone morphogenetic protein for the maintenance and stimulation of an osteoblast phenotype was examined using mouse MC3T3-E1 cell cultures. Cells expressed BMP-4 mRNA, which correlated with the stimulation of the osteoblast phenotype. The addition of a BMP-4 specific antibody reduced bone nodules, suggesting that BMP-4 is required for the osteogenic activity of osteoblasts in an autocrine manner. Exogenously added BMP-7 gradually decreased the expression of BMP-4 with a concurrent stimulation of the osteoblast phenotype. Exogenous BMP-7 can therefore substitute for endogenously produced BMP-4 acting as a paracrine factor on osteoblasts. The addition of 17beta estradiol decreased BMP-4 expression but initiated synthesis of BMP-6 mRNA, an endocrine signal for osteoblasts, which also substituted for the lack of endogenous BMP-4, as evidenced by normal bone nodule formation. The addition of dexamethasone and parathyroid hormone did not affect the BMP-4 expression but induced transcripts for BMP-2 and BMP-3, respectively, suggesting that their effects on bone can be in part achieved via the BMP signaling. These experiments support the requirement of a BMP for osteoblast differentiation and function, demonstrating for the first time that a BMP can functionally substitute for another BMP in an autocrine/paracrine manner or mediate a response to an endocrine action on osteoblasts.
Martinovic
Snjezana
S
Department of Anatomy, Zagreb Medical School, Zagreb, Croatia.
Borovecki
Fran
F
Miljavac
Vera
V
Kisic
Veronika
V
Maticic
Drazen
D
Francetic
Igor
I
Vukicevic
Slobodan
S
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055398:Bone Morphogenetic Protein 3; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055398:Bone Morphogenetic Protein 3; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004958:Estradiol; D003907:Dexamethasone