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

联合应用RANKL、M-CSF和CCN2可显著促进抗酒石酸酸性磷酸酶(TRAP)阳性多核细胞的形成。因此，我们怀疑CCN2参与了破骨细胞形成过程中的细胞-细胞融合。为了阐明这一机制，我们从出生14.5天的Ccn2基因缺失的小鼠中分离出胎肝细胞，并研究了TRAP阳性多核细胞的形成。结果表明，RANKL诱导的破骨细胞生成在Ccn2基因缺失的小鼠胎肝细胞中受到损害，外源性CCN2可以挽救受损的破骨细胞形成。这些结果表明，CCN2参与了破骨细胞形成过程中的细胞-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.