biostudies-literatureUnknown122Liu M<h4>Background</h4>Skeletal muscle-to-bone crosstalk may play critical roles in the association between muscle atrophy and bone loss. Here, we report a myokine, IL-33, which may mediate muscle-to-bone crosstalk.<h4>Methods</h4>A cohort study was conducted to elucidate the associations among circulating IL-33, osteoporosis, and sarcopenia in older adults. To delineate the role of IL-33 in muscle-to-bone crosstalk, we established rat models combining weighted-bearing exercise (WBE), botulinum neurotoxin A (BoNT/A)-induced muscle atrophy, and ovariectomy (OVX), and modulated muscle IL-33 levels both non-specifically and in a muscle-specific manner. Single-cell RNA sequencing was employed to identify the mechanisms by which IL-33 influences bone metabolism, and the downstream pathway was interEBioMedicine106024https://www.ebi.ac.uk/biostudies/studies/S-EPMC12661402biostudies-literatureSkeletal muscle-derived IL-33 mediates muscle-to-bone crosstalk and regulates bone metabolism via CD8&lt;sup&gt;+&lt;/sup&gt; T cell-secreted CCL5.PMC12661402Chu QLiu MZhu YZhang YHan YSun GWang JYang CChen BfalseSkeletal muscle-derived IL-33 mediates muscle-to-bone crosstalk and regulates bone metabolism via CD8&lt;sup&gt;+&lt;/sup&gt; T cell-secreted CCL5.<h4>Background</h4>Skeletal muscle-to-bone crosstalk may play critical roles in the association between muscle atrophy and bone loss. Here, we report a myokine, IL-33, which may mediate muscle-to-bone crosstalk.<h4>Methods</h4>A cohort study was conducted to elucidate the associations among circulating IL-33, osteoporosis, and sarcopenia in older adults. To delineate the role of IL-33 in muscle-to-bone crosstalk, we established rat models combining weighted-bearing exercise (WBE), botulinum neurotoxin A (BoNT/A)-induced muscle atrophy, and ovariectomy (OVX), and modulated muscle IL-33 levels both non-specifically and in a muscle-specific manner. Single-cell RNA sequencing was employed to identify the mechanisms by which IL-33 influences bone metabolism, and the downstream pathway was inter2025-01-01T00:00:00Z2025 Nov2026-06-05T20:46:42.392Z2026-05-21T03:13:03.89ZS-EPMC126614024123766910.1016/j.ebiom.2025.106024