Regulation of osteoclast function via Rho-Pkn3-c-Src pathways.
J Oral Biosci
; 61(3): 135-140, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31400545
ABSTRACT
BACKGROUND:
Wnt signaling pathways are largely divided into the ß-catenin-dependent canonical pathway and ß-catenin-independent non-canonical pathways. The roles of Wnt signaling in bone metabolism have been extensively investigated. We previously attempted to clarify the roles of Wnt-non-canonical signaling in bone resorption and demonstrated that Wnt5a-receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling promoted osteoclast differentiation by enhancing RANK expression in osteoclast precursor cells. However, the roles of Wnt5a-Ror2 signaling in osteoclast function remain unclear. HIGHLIGHT Trabecular bone mass was significantly greater in osteoclast-specific Ror2-deficient (Ror2ΔOCL/ΔOCL) mice than in control mice due to the decreased bone-resorbing activity of osteoclasts. Wnt5a-Ror2 signaling activated Rho in osteoclasts via dishevelled-associated activator of morphogenesis 2 (Daam2). The expression of protein kinase N3 (Pkn3), a Rho effector, increased during osteoclast differentiation. Trabecular bone mass was significantly greater in Pkn3-deficient mice than in wild-type mice due to the decreased bone-resorbing activity of osteoclasts. Pkn3 bound to c-Src and Pyk2 in a Wnt5a-Ror2 signaling-dependent manner, thereby enhancing the kinase activity of c-Src in osteoclasts. The binding of Pkn3 to c-Src was essential for the bone-resorbing activity of osteoclasts.CONCLUSION:
Wnt5a-Ror2 signaling promotes the bone-resorbing activity of osteoclasts by activating the Daam2-Rho-Pkn3-c-Src pathways. Pkn3 inhibitors, therefore, have potential as therapeutic agents for osteoporosis and bone destruction in inflammatory diseases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoclasts
/
Bone Resorption
Limits:
Animals
Language:
En
Journal:
J Oral Biosci
Year:
2019
Document type:
Article
Affiliation country:
Japón