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The canonical Wnt\/\u03b2\u2010catenin pathway is a master regulator of bone homeostasis; however, its role in the specialized environment of the alveolar bone\u2014marked by rapid turnover, complex mechanical forces, and exposure to the oral microbiome\u2014remains incompletely understood, particularly in the context of aging. This review critically synthesizes evidence on Wnt signaling in alveolar bone remodeling, with a focus on age\u2010related dysregulation, contrasting established paradigms from long bone biology with emerging oral\u2010tissue\u2010specific data. Wnt\/\u03b2\u2010catenin signaling is essential for periodontal homeostasis, orchestrating osteoblastogenesis and mechanotransduction. Its activity is compartment\u2010specific within the periodontium and is potently suppressed in pathology. Key mechanisms of age\u2010related decline include the upregulation of Wnt antagonists (e.g., sclerostin, DKK1), cellular senescence, altered FoxO\u2013Wnt crosstalk under oxidative stress, and impaired mechanosensing. These changes converge to disrupt regenerative capacity, tipping the balance toward net alveolar bone loss. Therapeutically, sclerostin inhibition demonstrates robust preclinical efficacy in rescuing bone loss in models of periodontitis and estrogen deficiency. However, the potential cardiovascular risks of systemic Wnt activation suggest that redirecting efforts toward localized delivery strategies could be a promising alternative. Aging induces a multifaceted suppression of regenerative Wnt signaling in the periodontium. Modulating the Wnt pathway shows great potential for oral bone regeneration. However, significant challenges exist, especially in designing local delivery systems that are both safe and effective. Overcoming these hurdles is crucial for successful clinical applications. Future research must bridge the gap between skeletal biology and direct oral\u2010specific investigations to enable targeted therapies that preserve periodontal health in an aging population.<\/jats:p>","DOI":"10.1111\/jre.70085","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:00:26Z","timestamp":1770206426000},"page":"237-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Wnt Signaling in Age\u2010Related Alveolar Bone Loss and Regeneration"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-3838","authenticated-orcid":false,"given":"Hsiao H.","family":"Sung","sequence":"first","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Oral and Maxillofacial Surgery University of Michigan  Ann Arbor Michigan USA"},{"name":"Experimental Rheumatology, Department of Rheumatology Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navya","family":"Chalamalasetty","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alzainal","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlong","family":"Liu","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lexuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietra Colacrai","family":"Arikita","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy C. X.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences &amp; Prosthodontics University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-1799","authenticated-orcid":false,"given":"Hom\u2010Lay","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. H. J.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology, Department of Rheumatology Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S.","family":"Caird","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van der Kraan","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology, Department of Rheumatology Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-7258","authenticated-orcid":false,"given":"Kenneth M.","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic 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