ArticleMedComm2026
Ciliary Ift20 and Wwtr1 Coordinate Transforming Growth Factor-β Receptor II Signaling to Maintain Bone-Fat Balance in Skeletal Homeostasis.
Article in MedComm, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The balance between bone formation and bone marrow adipose tissue accumulation is essential for skeletal integrity, and disruption of this balance contributes to skeletal degeneration, osteoporosis, and metabolic bone loss. However, the molecular mechanisms controlling this balance across skeletal homeostasis and disease remain unclear. Here, transcriptomic analysis of human osteoporotic bone samples revealed significant downregulation of Ift20 and Wwtr1 in osteoblast-lineage cells. Using osteoblast-specific knockout models, we found that loss of both Ift20 and Wwtr1 in the osteoblast lineage caused severe bone loss and excessive bone marrow adipose tissue accumulation, which was further aggravated under ovariectomy and high-fat diet conditions. Mechanistically, Ift20 localized to primary cilia and interacted with transforming growth factor-β receptor II (TβRII), protecting it from c-Cbl-mediated ubiquitination and degradation to sustain TGF-β signaling. Meanwhile, Wwtr1 directly bound the
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