Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-κB

Area of Science:

• Bone biology
• Immunology
• Endocrinology

Background:

• Aging-related bone loss and osteoporosis are significant global health issues.
• Chronic inflammation exacerbates bone resorption and hinders bone formation.
• Nuclear factor-kappa B (NF-κB) signaling is implicated in age-related bone pathologies.

Purpose of the Study:

• To investigate the role of Wnt4 in attenuating bone loss in osteoporosis and skeletal aging.
• To elucidate the mechanism by which Wnt4 affects bone metabolism and inflammation.
• To evaluate Wnt4 as a potential therapeutic target for bone diseases.

Main Methods:

• Utilized transgenic mice expressing Wnt4 in osteoblasts.
• Induced bone loss models using ovariectomy and tumor necrosis factor.
• Administered recombinant Wnt4 in vivo.
• Assessed NF-κB activation and osteoclastogenesis.

Main Results:

• Wnt4 expression protected mice from ovariectomy-, TNF-, and aging-induced bone loss and inflammation.
• Wnt4 promoted bone formation and inhibited osteoclast formation and bone resorption.
• Wnt4 inhibited NF-κB activation via transforming growth factor-β-activated kinase-1 (Tak1) independently of β-catenin.
• Recombinant Wnt4 alleviated bone loss and inflammation in vivo.

Conclusions:

• Wnt4 signaling, through noncanonical pathways, inhibits NF-κB and attenuates bone loss.
• Wnt4 demonstrates a dual role in promoting bone formation and inhibiting bone resorption.
• Wnt4 represents a promising therapeutic target for osteoporosis and skeletal aging.