| First Author | Wang T | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 2 | Pages | 108857 |
| PubMed ID | 38303710 | Mgi Jnum | J:351644 |
| Mgi Id | MGI:7581690 | Doi | 10.1016/j.isci.2024.108857 |
| Citation | Wang T, et al. (2024) Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9. iScience 27(2):108857 |
| abstractText | The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (Rheb(BAD) KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-kappaB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from Rheb(BAD) KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the Rheb(BAD) KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis. |
