〔Abstract〕 Objective To explore the effect of miR-23b-3p regulation on osteogenic differentiation of renal interstitial fibroblasts(hRIFs) on the formation of Randall plaque and its possible mechanism. Methods qRT-PCR was used to detect the expression levels of miR-23b-3p and osteogenic marker: myocyte enhancer factor 2C(MEF2C), osteocalcin(OCN), osteopontin(OPN), runt-related transcription factor 2(Runx2) mRNA in Randall plaque tissue of CaOx stone patients(RP) and normal papillary tissue of kidney tumor patients undergoing nephrectomy(nRP). Isolation and culture of human normal hRIFs were isolated and cultured in vitro. The miR-23b-3p overexpression plasmid pSi-miR-23b-3p and its negative no-load plasmid pSi-NC, the MEF2C lentivirus overexpression plasmid Lv-MEF2C and the no-load plasmid Lv-NC were transfected into hRIFs cells, and the cells were induced to osteogenic differentiation for 14 days. The activity of alkaline phosphatase(ALP) was determined by ELISA. Alizarin red staining was used to observe the formation of mineralized nodules. The expression levels of miR-23b-3p and MEF2C, OCN, OPN, Runx2 mRNA were detected by qRT-PCR. The expression level of MEF2C protein was detected by Western blot. Dual luciferase reporter gene assay verified the targeting relationship between miR-23b-3p and MEF2C. Results (1) Compared with the nRP group, miR-23b-3p was low expressed and MEF2C, OCN, OPN, and Runx2 were highly expressed in the RP group.(2) 14 days after osteogenic induction of hRIFs cells, the activity of ALP in cells significantly increased, the ability of cells to form mineralized nodules was enhanced, the expression level of miR-23b-3p significantly decreased, the mRNA expression levels of MEF2C, OCN, OPN, and Runx2 significantly increased, and the expression level of MEF2C protein significantly increased.(3) Overexpression of miR-23b-3p decreased the activity of ALP in hRIFs cells after osteogenic induction, inhibited the formation of mineralized nodules in cells, and down-regulated the mRNA expression levels of OCN, OPN, and Runx2 in cells.(4) Overexpression of MEF2C reversed the inhibitory effect of miR-23b-3p overexpression on osteoblast differentiation of hRIFs cells.(5) MEF2C was the downstream target gene of miR-23b-3p. Conclusion miR-23b-3p is underexpressed in RP tissues and during osteoblastic differentiation of hRIFs cells. Up-regulation of miR-23b-3p inhibits osteogenic differentiation of hRIFs cells, and its mechanism may be related to targeted silencing MEF2C.