Clarification of molecular mechanism on the osteoclastogenesis promoted by CCN family 2/connective tissue growth factor

与RANKL和M-CSF相比，RANKL、M-CSF和CCN2联合使用显著增强了酒石酸抗性酸性磷酸酶（TRAP）阳性的多核细胞形成。因此，我们怀疑在破骨细胞形成过程中，CCN2参与了细胞-细胞融合。为了阐明这一机制，我们在E14.5天分离了ccn2缺失小鼠的胎儿肝细胞，并研究了trap阳性的多核细胞形成。结果表明，rankl诱导的CCN2缺失小鼠胎肝细胞破骨细胞形成受损，添加外源性CCN2可恢复受损的破骨细胞形成。这些结果表明，在破骨细胞形成过程中，CCN2参与了细胞-细胞融合。

Combination of RANKL, M-CSF and CCN2 significantly enhanced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation compared with RANKL and M-CSF. Therefore, we suspected the involvement of CCN2 in cell-cell fusion during osteoclastogenesis. To clarify the mechanism, we isolated fetal liver cells from Ccn2-null mice at E14.5 days, and investigated TRAP-positive multinucleated cell formation. The results showed that RANKL-induced osteoclastogenesis was impaired in fetal liver cells from Ccn2-null mice, and the impaired osteoclast formation was rescued by the addition of exogenous CCN2. These results suggest that CCN2 involves in cell-cell fusion during osteoclastogenesis.