Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation.
Direct cell-cell interactions are fundamental for tissue development and differentiation. We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation. Using reverse transcription-polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-11 (C11) and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4 (C4) mRNA. C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein-2 (BMP-2) treatment of either BMCs or HOBs. Likewise, N-cad mRNA did not change during BMP-2 incubation. Conversely, C4 protein, undetectable in transformed cell lines, was down-regulated by BMP-2 treatment of normal cells. Both C11 and C4 were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated by a beta-catenin antibody, findings indicative of functional cadherins. A decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+-dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins. Cadherin-mediated cell-to-cell adhesion is critical for normal human osteoblast differentiation.
Cheng
S L
SL
Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Lecanda
F
F
Davidson
M K
MK
Warlow
P M
PM
Zhang
S F
SF
Zhang
L
L
Suzuki
S
S
St John
T
T
Civitelli
R
R
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000378:metabolism*; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D051176:beta Catenin
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051176:beta Catenin