Inhibitory effects of activin-A on osteoblast differentiation during cultures of fetal rat calvarial cells.
Activin-A is a member of the transforming growth factor-beta (TGF-beta) superfamily and is expressed by osteoblasts. However, the role of activin-A on osteoblasts is not clearly understood. We examined the effects of activin-A on osteoblast proliferation or differentiation, and mineralization by the osteoblasts in the first subcultures of fetal rat osteoblasts obtained from calvarial bones. Exogenous activin-A led to impaired formation of bone nodules in a dose-dependent manner, although it did not influence cell proliferation using an MTT assay. This inhibitory effect depended upon the time at which activin-A was added to the culture media, and the effect was most significant when addition took place at the early phase of the culture. In addition, exogenous activin-A inhibited gene expression of type I procollagen, alkaline phosphatase, osteonectin, and osteopontin in the cultured cells using Northern blot analysis. The peak of osteocalcin mRNA was delayed. Gene expression for TGF-beta was not influenced by exogenous activin-A. The betaA subunit (activin-A) mRNA was detected during the early phase of this culture. These results indicate that activin-A inhibited early differentiation of the fetal rat calvarial cells, or osteoblasts.
Ikenoue
T
T
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Jingushi
S
S
Urabe
K
K
Okazaki
K
K
Iwamoto
Y
Y
D028341:Activins; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007265:Inhibins / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000494:pharmacology; D015676:Osteonectin / Q000494:pharmacology; D053495:Osteopontin; D011347:Procollagen / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology; D012886:Skull / Q000187:drug effects* / Q000196:embryology; D013997:Time Factors
D015676:Osteonectin; D011347:Procollagen; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D028341:Activins; D015675:Osteocalcin; D053495:Osteopontin; D007265:Inhibins; D000469:Alkaline Phosphatase