LncRNA HAGLR accelerates femoral neck fracture healing through negatively regulating miRNA-19a-3p

L.-X. Pan, W. Ding

Department of Orthopedics, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China. weiding0910@126.com

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• Orthopedics

OBJECTIVE: This study aims to uncover the function of long non-coding RNA (lncRNA) HAGLR in the healing process of femoral neck fracture and the underlying mechanism.

PATIENTS AND METHODS: Expression levels of HAGLR, microRNA-19a-3p (miRNA-19a-3p) and TGFBR2 in fractured femoral neck tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Regulatory effects of HAGLR on viability, apoptosis, migration, and protein levels of BALP and Osteocalcin in MC3T3-E1 cells were determined. Dual-Luciferase reporter gene assay was conducted to assess the binding in HAGLR/miRNA-19a-3p/TGFBR2. In addition, relative levels of TGFBR2, p-smad2, p-smad3, and RUNX2 in MSCs influenced by HAGLR were detected.

RESULTS: HAGLR was downregulated in fractured femoral neck tissues. Knockdown of HAGLR reduced viability and migration, enhanced apoptotic rate, as well as downregulated BALP and Osteocalcin in MC3T3-E1 cells. HAGLR served as miRNA-19a-3p sponge, and miRNA-19a-3p directly targeted 3ʹ-untranslated region (3ʹ-UTR) of TGFBR2. Knockdown of HAGLR downregulated expressions of TGFBR2, p-smad2, p-smad3, and RUNX2 in MC3T3-E1 cells, indicating the inhibited TGF-β pathway.

CONCLUSIONS: LncRNA HAGLR/miRNA-19a-3p/TGFBR2 regulatory loop accelerates the healing process of femoral neck fracture by inhibiting the TGF-β pathway.

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