LncRNA FGF13-AS1 predicts delayed fracture healing and promotes osteoporotic fracture healing by regulating miR-128-3p/CBFB-mediated osteogenesis and osteoclast activity.

OBJECTIVE

Osteoporotic fracture (OPF) disrupts bone homeostasis via resorption-formation imbalance. This study investigates the expression and role of the long non-coding RNA FGF13 antisense RNA 1 (FGF13-AS1) in OPF bone healing.

METHODS

Recruited 110 patients with osteoporosis (OP) and 138 patients with OPF and 90 healthy people, then divided OPF patients into normal healing (NFH) and delayed healing groups (DFH) after a 4-month follow-up. In vitro, MC3T3-E1 cells undergo osteogenic differentiation while RAW264.7 cells undergo osteoclastogenic differentiation. Serum FGF13-AS1 and miR-128-3p levels were determined by real-time quantitative reverse transcription PCR (RT-qPCR). The receiver operating characteristic (ROC) curve assessed FGF13-AS1's diagnostic value for OP. Logistic regression pinpointed potential risk factors for DFH. Cell counting kit-8 (CCK-8) and flow cytometry assays were used to determine cell proliferation and apoptosis. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activity were measured via commercial kits. RT-qPCR evaluated expression of osteogenic and osteoclast differentiation markers.

RESULTS

Serum FGF13-AS1 levels decline significantly in OP patients, particularly in OPF cases. DFH patients have lower levels than NFH patients. Low FGF13-AS1 expression predicts DFH and is a potential risk factor for its onset. MC3T3-E1 cells in osteoblastic differentiation showed marked upregulation of FGF13-AS1 and core-binding factor subunit β (CBFB) and downregulation of miR-128-3p. FGF13-AS1 overexpression enhanced ALP activity, osteogenic marker expression, and cell proliferation, and suppressed apoptosis; miR-128-3p effectively reversed these effects. During osteoclast differentiation, FGF13-AS1 and CBFB decreased, and miR-128-3p increased. Inhibition of FGF13-AS1 elevated TRAP activity and osteoclast differentiation markers. This effect was markedly mitigated by reducing miR-128-3p levels.

CONCLUSION

Low FGF13-AS1 serves as a marker for delayed fracture healing in osteoporosis. It likely acts via the miR-128-3p/CBFB axis to balance osteogenic differentiation and promote bone formation. Deficiency of FGF13-AS1 may contribute to delayed healing and represents a potential clinical molecular target.