LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression

R.-F. Zhang, J.-W. Liu, S.-P. Yu, D. Sun, X.-H. Wang, J.-S. Fu, Z. Xie

National & Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China. xiezhao54981@163.com

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• Orthopedics

OBJECTIVE: The aim of this study was to detect the expression of long non-coding ribonucleic acid (lncRNA) urothelial carcinoma associated 1 (UCA1) in the plasma of patients with osteoporosis (OST), and to investigate its influences on the proliferation and differentiation of osteoblasts and its mechanism.

PATIENTS AND METHODS: Plasma samples were collected from 52 OST patients treated in our hospital and 30 healthy subjects receiving a physical examination, respectively. The expression level of lncRNA UCA1 in OST patients and healthy subjects were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Furthermore, osteoblast MC3T3-E1 cell lines with a stable knockout of UCA1 in mice were constructed using small-interfering RNA (siRNA). The influence of UCA1 knockout on the proliferation of osteoblasts was detected using cell counting kit-8 (CCK-8) assay. Meanwhile, the proportion of EdU-positive cells in osteoblasts of the control group and UCA1 knockout group was detected using EdU staining. Moreover, the messenger RNA (mRNA) levels of differentiation-related genes, including Runt-related transcription factor 2 (Runx2), Collagen1α1, osteoclast (OC), osteoprotegerin (OPG), osteopontin (OPN) and Osterix (OSX), were detected via RT-PCR. The protein expression level of Runx2 was detected via Western blotting. In addition, osteoblasts were cultured with a bone-derived medium for 14 d. Then, the differentiation status was detected via alizarin red staining and alkaline phosphatase staining. Finally, the expression of bone morphogenetic protein-2 (BMP-2)/(Smad1/5/8) signaling pathway was analyzed using Western blotting.

RESULTS: The expression of plasma lncRNA UCA1 was significantly increased in OST patients (p<0.05). Cell experiments revealed that UCA1 siRNA intervention could significantly promote the proliferation and differentiation of osteoblast MC3T3-E1 cell lines. In addition, Western blotting showed that the pro-apoptotic effect of UCA1 might be mediated by the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts.

CONCLUSIONS: Inhibiting lncRNA UCA1 can promote the proliferation and differentiation of osteoblasts by activating the BMP-2/(Smad1/5/8) signaling pathway in osteoblasts. Therefore, UCA1 is expected to be a new therapeutic target for OST.

This article has been retracted. The Publisher apologizes for any inconvenience this may cause. Retraction note in: Eur Rev Med Pharmacol Sci 2024; 28 (11): 3701-3701.

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