TY - JOUR
T1 - Osteocalcin promotes proliferation, differentiation, and survival of PC12 cells
AU - Ando, Eika
AU - Higashi, Sen
AU - Mizokami, Akiko
AU - Watanabe, Seiji
AU - Hirata, Masato
AU - Takeuchi, Hiroshi
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grants ( 17K11649 to H.T., 18K09510 to S. H., 18K09521 to A.M., and 17K19766 , 17H01595 and 20H03854 to M.H.). We would like to thank Editage ( www.editage.com ) for English language editing.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6/11
Y1 - 2021/6/11
N2 - Involvement of the bone matrix protein osteocalcin (OC) in the development of learning and memory, and the prevention of anxiety-like behaviors in mice. However, the direct effects of OC on neurons are still unknown comparing to the mechanism how OC affects systemic energy expenditure and glucose homeostasis. In this study, we investigated the effect of OC on proliferation, differentiation, and survival of neurons using the rat pheochromocytoma cell line PC12. RT-PCR analysis for OC receptor candidates revealed that Gpr158, but not Gprc6a, mRNA was expressed in PC12 cells. The growth of PC12 cells cultured in the presence of 5–50 ng/mL of either uncarboxylated (GluOC) or carboxylated (GlaOC) OC was increased compared to cells cultured in the absence of OC. In addition, NGF-induced neurite outgrowth was enhanced by OC, and H2O2-induced cell death was suppressed by pretreatment with OC. All of these results were observed for both GluOC and GlaOC at comparable levels, suggesting that OC may directly affect cell proliferation, differentiation, and survival by binding to its candidate receptor, GPR158.
AB - Involvement of the bone matrix protein osteocalcin (OC) in the development of learning and memory, and the prevention of anxiety-like behaviors in mice. However, the direct effects of OC on neurons are still unknown comparing to the mechanism how OC affects systemic energy expenditure and glucose homeostasis. In this study, we investigated the effect of OC on proliferation, differentiation, and survival of neurons using the rat pheochromocytoma cell line PC12. RT-PCR analysis for OC receptor candidates revealed that Gpr158, but not Gprc6a, mRNA was expressed in PC12 cells. The growth of PC12 cells cultured in the presence of 5–50 ng/mL of either uncarboxylated (GluOC) or carboxylated (GlaOC) OC was increased compared to cells cultured in the absence of OC. In addition, NGF-induced neurite outgrowth was enhanced by OC, and H2O2-induced cell death was suppressed by pretreatment with OC. All of these results were observed for both GluOC and GlaOC at comparable levels, suggesting that OC may directly affect cell proliferation, differentiation, and survival by binding to its candidate receptor, GPR158.
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U2 - 10.1016/j.bbrc.2021.03.146
DO - 10.1016/j.bbrc.2021.03.146
M3 - Article
C2 - 33865226
AN - SCOPUS:85104060522
SN - 0006-291X
VL - 557
SP - 174
EP - 179
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -