LncRNA PRNCR1 regulates CXCR4 expression to affect osteogenic differentiation and contribute to osteolysis after hip
Zong-Ming Gong1, Zhen-Yu Tang1, Xiao-Liang Sun1
1Department of Articular Orthopaedics, Changzhou First People's Hospital, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Background:
Osteogenic differentiation plays an essential role in the pathogenesis of osteolysis, which is a complication of hip orthroplasty. The roles of lncRNA PRNCR1 in osteogenic differentiation and osteolysis were dissected in this study.
Methods:
The expression of PRNCR1, miR-211-5p and C-X-C chemokine receptor-4 (CXCR4) protein in wear particles and mesenchymal stem cells (MSCs) were determined by qRT-PCR and Western blot, separately. The osteogenic differentiation degree of MSCs was assessed by ALP activity detection and ARS staining. Binding and interaction between RNA and protein were determined with RIP and RNA pull-down assay, respectively. Interaction between miR-211-5p and CXCR4 was examined by Dual luciferase reporter assay.
Results:
PRNCR1 and CXCR4 were up-regulated in wear particles around prosthesis and in MSCs treated with PMMA, while miR-211-5p was down-regulated. Repression of PRNCR1 weakened the inhibitory effect of wear particles on osteogenic differentiation. PRNCR1 positively regulated CXCR4 through inhibiting miR-211-5p. Wear particles increased CXCR4 level through miR-211-5p to inhibit osteogenic differentiation of MSCs. Wear particles down-regulated miR-211-5p level through PRNCR1 to influence osteogenic differentiation of MSCs.
Conclusion:
LncRNA PRNCR1 up-regulates CXCR4 through targeting miR-211-5p, which affects osteogenic differentiation and thus contributing to osteolysis after hip replacement.
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