| First Author | Safari F | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 5 | PubMed ID | 38388173 |
| Mgi Jnum | J:345968 | Mgi Id | MGI:7609242 |
| Doi | 10.26508/lsa.202302297 | Citation | Safari F, et al. (2024) SHIP1 deficiency causes inflammation-dependent retardation in skeletal growth. Life Sci Alliance 7(5) |
| abstractText | Inflammation and skeletal homeostasis are closely intertwined. Inflammatory diseases are associated with local and systemic bone loss, and post-menopausal osteoporosis is linked to low-level chronic inflammation. Phosphoinositide-3-kinase signalling is a pivotal pathway modulating immune responses and controlling skeletal health. Mice deficient in Src homology 2-containing inositol phosphatase 1 (SHIP1), a negative regulator of the phosphoinositide-3-kinase pathway, develop systemic inflammation associated with low body weight, reduced bone mass, and changes in bone microarchitecture. To elucidate the specific role of the immune system in skeletal development, a genetic approach was used to characterise the contribution of SHIP1-controlled systemic inflammation to SHIP1-dependent osteoclastogenesis. Lymphocyte deletion entirely rescued the skeletal phenotype in Rag2 (-/-) /Il2rg (-/-) /SHIP1 (-/-) mice. Rag2 (-/-) /Il2rg (-/-) /SHIP1 (-/-) osteoclasts, however, displayed an intermediate transcriptomic signature between control and Rag2 (+/+) /Il2rg (+/+) /SHIP1 (-/-) osteoclasts while exhibiting aberrant in vitro development and functions similar to Rag2 (+/+) /Il2rg (+/+) /SHIP1 (-/-) osteoclasts. These data establish a cell-intrinsic role for SHIP1 in osteoclasts, with inflammation as the key driver of the skeletal phenotype in SHIP1-deficient mice. Our findings demonstrate the central role of the immune system in steering physiological skeletal development. |
