Regulator of G protein signalling 18 promotes osteocyte proliferation by activating the extracellular signal‑regulated kinase signalling pathway

Meng,Yong; Qiu,Si-Qiang; Wang,Qiang; Zuo,Jin-Liang

doi:10.3892/ijmm.2024.5346

Regulator of G protein signalling 18 promotes osteocyte proliferation by activating the extracellular signal‑regulated kinase signalling pathway

Authors:
- Yong Meng
- Si-Qiang Qiu
- Qiang Wang
- Jin-Liang Zuo
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Affiliations: Department of Orthopaedics, The Fifth Affiliated Hospital Jinan University, Heyuan, Guangdong 517000, P.R. China, Department of Spine Surgery, The Fourth People's Hospital of Jinan, Jinan, Shandong 250031, P.R. China
Published online on: January 8, 2024 https://doi.org/10.3892/ijmm.2024.5346
Article Number: 22
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteocyte function is critical for metabolism, remodelling and regeneration of bone tissue. In the present study, the roles of regulator of G protein signalling 18 (RGS18) were assessed in the regulation of osteocyte proliferation and bone formation. Target genes and signalling pathways were screened using the Gene Expression Omnibus (GEO) database and Gene Set Enrichment Analysis (GSEA). The function of RGS18 and the associated mechanisms were analysed by Cell Counting Kit 8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, reverse transcription‑quantitative PCR, western blotting and immunostaining. Overlap analysis of acutely injured subjects (AIS) and healthy volunteers (HVs) from the GSE93138 and GSE93215 datasets of the GEO database identified four genes: KIAA0825, ANXA3, RGS18 and LIPN. Notably, RGS18 was more highly expressed in peripheral blood samples from AIS than in those from HVs. Furthermore, RGS18 overexpression promoted MLO‑Y4 and MC3T3‑E1 cell viability, proliferation and S‑phase arrest, but inhibited apoptosis by suppressing caspase‑3/9 cleavage. Silencing RGS18 exerted the opposite effects. GSEA of GSE93138 revealed that RGS18 has the ability to regulate MAPK signalling. Treatment with the MEK1/2 inhibitor PD98059 reversed the RGS18 overexpression‑induced osteocyte proliferation, and treatment with the ERK1/2 activator 12‑O‑tetradecanoylphorbol‑13‑acetate reversed the effects of RGS18 silencing on osteocyte proliferation. In conclusion, RGS18 may contribute to osteocyte proliferation and bone fracture healing via activation of ERK signalling.

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