Elevated expression of CTRP3/cartducin contributes to promotion of osteosarcoma cell proliferation.

CTRP3/cartducin, a novel secretory protein, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily, and plays important roles in regulating both embryonic cartilage development and postnatal longitudinal bone growth. CTRP3/cartducin is expressed in human osteosarcomas. We hypothesized that CTRP3/cartducin might have a role in osteosarcoma tumor growth and metastasis. Murine osteosarcoma cell lines, NHOS and LM8, were used as a model. RT-PCR analysis showed that the mRNA level of CTRP3/cartducin was increased in these two murine osteosarcoma cell lines compared with its level in normal murine osteoblast MC3T3-E1 cells. Western blot analysis showed that the protein level of CTRP3/cartducin was also increased in these two osteosarcoma cell lines. Stimulation of NHOS and LM8 cells by CTRP3/cartducin promoted tumor cell growth but not migration in vitro. Further, CTRP3/cartducin stimulation led to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in these two osteosarcoma cell lines. MAPK/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, blocked CTRP3/cartducin-induced cell proliferation. These results suggest that CTRP3/cartducin expression may play a role in osteosarcoma tumor growth associated with activation of the ERK1/2 signaling pathway.