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PubMed · 42296055

The HOXA gene cluster: a critical regulator in bone-related disorders.

Yangyang Zhang·Lewei Zhang·Yi Li·Jia Bai·Haihong Lv
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Abstract

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

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HumansHomeodomain ProteinsMultigene FamilyEpigenesis, GeneticAnimalsBone DiseasesOsteogenesisOsteoporosisSignal TransductionGenes, HomeoboxRNA, UntranslatedHOXA familybone developmentbone metabolismepigenetic regulationfracture healingnon-coding RNAosteoporosisJournal ArticleReviewResearch Support, Non-U.S. Gov't

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Yangyang Zhang, Lewei Zhang, Yi Li, Jia Bai, Haihong Lv. 2026-06-15. The HOXA gene cluster: a critical regulator in bone-related disorders.. https://doi.org/10.1080/07853890.2026.2685993

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Animals subjectBone Development subjectEpigenesis, Genetic subjectFracture Healing subjectHumans subjectJournal Article subjectMultigene Family subject

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