Abstract
βig-h3 is an extracellular matrix (ECM) protein induced by TGF-β, and it has motifs interacting with the α3β1, αvβ5, and αvβ3 integrins. Our previous study shows the role of βig-h3 in osteoblast differentiation and its involvement in melorheostosis, a rare bone disease. Here we demonstrate that βig-h3 expression is down-regulated during the early stage of differentiation of the murine preosteoblastic cell line, KS483. The recombinant βig-h3 and its FAS1 domain significantly inhibited in vitro osteoblast differentiation as evaluated by matrix mineralization/bone nodule formation. Furthermore, inhibition of expression of osteoblast differentiation marker genes [such as type I collagen, alkaline phosphatase, and osteocalcin (OC)] was accompanied by suppression of osteoblast-specific transcription factors, Cbfa1/Runx2 and osterix. Flow cytometric analyses, cell adhesion, and inhibition assays disclosed αvβ3 and αvβ5 as the principal integrins mediating the adhesion of osteoblastic cells to βig-h3. The disruption of interactions between βig-h3 and osteoblasts by a function-blocking antibody specific for αvβ3 but not for αvβ5 abolished the inhibitory effect of βig-h3 on osteoblast differentiation. We suggest that these interacting integrins may play an important role in βig-h3-mediated inhibition of osteoblast differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 232-242 |
| Number of pages | 11 |
| Journal | Bone |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2005 Jan 1 |
| Externally published | Yes |
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Keywords
- Bone formation
- Osteoblast differentiation
- TGF-β
- αvβ3/β5 integrin
- βig-h3
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology
Cite this
βig-h3 mediates osteoblast adhesion and inhibits differentiation. / Thapa, Narendra; Kang, Kae Bok; Kim, In-San.
In: Bone, Vol. 36, No. 2, 01.01.2005, p. 232-242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - βig-h3 mediates osteoblast adhesion and inhibits differentiation
AU - Thapa, Narendra
AU - Kang, Kae Bok
AU - Kim, In-San
PY - 2005/1/1
Y1 - 2005/1/1
N2 - βig-h3 is an extracellular matrix (ECM) protein induced by TGF-β, and it has motifs interacting with the α3β1, αvβ5, and αvβ3 integrins. Our previous study shows the role of βig-h3 in osteoblast differentiation and its involvement in melorheostosis, a rare bone disease. Here we demonstrate that βig-h3 expression is down-regulated during the early stage of differentiation of the murine preosteoblastic cell line, KS483. The recombinant βig-h3 and its FAS1 domain significantly inhibited in vitro osteoblast differentiation as evaluated by matrix mineralization/bone nodule formation. Furthermore, inhibition of expression of osteoblast differentiation marker genes [such as type I collagen, alkaline phosphatase, and osteocalcin (OC)] was accompanied by suppression of osteoblast-specific transcription factors, Cbfa1/Runx2 and osterix. Flow cytometric analyses, cell adhesion, and inhibition assays disclosed αvβ3 and αvβ5 as the principal integrins mediating the adhesion of osteoblastic cells to βig-h3. The disruption of interactions between βig-h3 and osteoblasts by a function-blocking antibody specific for αvβ3 but not for αvβ5 abolished the inhibitory effect of βig-h3 on osteoblast differentiation. We suggest that these interacting integrins may play an important role in βig-h3-mediated inhibition of osteoblast differentiation.
AB - βig-h3 is an extracellular matrix (ECM) protein induced by TGF-β, and it has motifs interacting with the α3β1, αvβ5, and αvβ3 integrins. Our previous study shows the role of βig-h3 in osteoblast differentiation and its involvement in melorheostosis, a rare bone disease. Here we demonstrate that βig-h3 expression is down-regulated during the early stage of differentiation of the murine preosteoblastic cell line, KS483. The recombinant βig-h3 and its FAS1 domain significantly inhibited in vitro osteoblast differentiation as evaluated by matrix mineralization/bone nodule formation. Furthermore, inhibition of expression of osteoblast differentiation marker genes [such as type I collagen, alkaline phosphatase, and osteocalcin (OC)] was accompanied by suppression of osteoblast-specific transcription factors, Cbfa1/Runx2 and osterix. Flow cytometric analyses, cell adhesion, and inhibition assays disclosed αvβ3 and αvβ5 as the principal integrins mediating the adhesion of osteoblastic cells to βig-h3. The disruption of interactions between βig-h3 and osteoblasts by a function-blocking antibody specific for αvβ3 but not for αvβ5 abolished the inhibitory effect of βig-h3 on osteoblast differentiation. We suggest that these interacting integrins may play an important role in βig-h3-mediated inhibition of osteoblast differentiation.
KW - Bone formation
KW - Osteoblast differentiation
KW - TGF-β
KW - αvβ3/β5 integrin
KW - βig-h3
UR - http://www.scopus.com/inward/record.url?scp=14144251874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14144251874&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2004.08.007
DO - 10.1016/j.bone.2004.08.007
M3 - Article
C2 - 15780949
AN - SCOPUS:14144251874
VL - 36
SP - 232
EP - 242
JO - Bone
JF - Bone
SN - 8756-3282
IS - 2
ER -