Effect of La^3＋ on osteoblastic differentiation of rat bone marrow stromal cells

Lanthanides are increasingly used in industry and agriculture in recent years. These applications increase the accumulation of lanthanides in the human body, especially in bone1]. Thus, people paid extensive atten-tion to the effect of lanthanides on bon…

Effect of La3+ on osteoblastic differentiation of rat bone marrow stromal cells

In the present work, the effect of La3 on osteoblastic differentiation of primary rat bone mar- row stromal cells (MSCs) as well as the related mechanisms are studied. Differentiation is monitored by detection of alkaline phosphatase (ALP) activity, osteocalcin secretion, the mRNA levels of Type I collagen and osteocalcin, and matrix mineralization. The results show that La3 inhibits osteoblastic differentiation of MSCs in the early and middle stages of culture, as demonstrated by the decrease of ALP activity, osteocalcin secretion, and down-regulation of the mRNA level of osteocalcin. However, La3 does not affect the matrix mineralization in advanced MSCs, because it up-regulates the mRNA levels of Type I collagen, and promotes ALP activity and os- teocalcin secretion in MSCs in the late stage of cul- ture. In addition, Western blot analysis exhibits that La3 induces the phosphorylation and activation of mitogen-activated protein kinase (MAPK). Further- more, MAPK kinase inhibitor PD98059 completely blocks the inhibitory effect of La3 on ALP activity of MSCs in the middle stage of culture. These results suggest that La3 affects MSCs osteoblastic differen- tiation depending on differentiation stages. La3 in- hibits osteoblastic differentiation of MSCs in the early and middle stages by a MAPK-dependent mecha- nism, but does not affect the matrix mineralization in advanced MSCs.