Different effects of Wnt/β-catenin activation and PTH activation in adult and aged male mice metaphyseal fracture healing

Wnt/β-catenin激活和PTH激活对成年和老年雄性小鼠干骺端骨折愈合的不同影响

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Abstract

BACKGROUND: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/β-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths. METHODS: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnb(lox(ex3)) mice and wild-type mice. The fracture healing effects of CA (Wnt/β-catenin activation) and PTH (activated by PTH (1-34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of β-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase). RESULT: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice. CONCLUSION: The application of Wnt/β-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.

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