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Abstract Objective The abnormal proliferation of osteoblasts leads to decreased bone mass，which is an important reason for the occurrence and development of osteoporosis.A large number of studies have found that Orai1 plays a very important role in regulating osteoblast proliferation and apoptosis.STIM1 is an important protein that can activate Orai1.However，there is no relevant report on whether STIM1 is involved in the regulation of osteoblast proliferation The purpose of this study was to determine the role of STIM1 in regulating osteoblast proliferation in osteoblasts.Methods After STIM1 knockdown，cell proliferation and cell cycle，the transcription of CyclinD1，CyclinE，CDK4 and CDK6，and Ras signaling pathway activity were tested to identify whether STIM1 is involved in the regulation of osteoblast proliferations.Results STIM1 was knockdown successfully after STIM1 siRNA transfected in MC3T3-E1 cells(P＜0.05).We found that the proliferation were decreased and cell cycle were arrested after STIM1 knockdown(P＜0.05).Furthermore，we found that the transcription of CyclinD1 was decreased after STIM1 knockdown(P＜0.05).We also found that Ras signaling pathway activity were inhibited(P＜0.05).The inhibition of Ras signaling pathway activity by ars-853 significantly inhibited the role of STIM1 in promoting the proliferation of osteoblasts(P＜0.05).Conclusion The results identified that STIM1 may activate Ras signaling pathway，thus regulating osteoblast proliferation.
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