JAK2-IGF1 axis in osteoclasts regulates postnatal growth in mice

• DOI: 10.1172/jci.insight.137045
• Publication Date: 2021-03-07T19:01:15Z
• Authors: David W. Dodington; Jenalyn L. Yumol; Jiaqi Yang; Evan Pollock-Tahiri; Tharini Sivasubra...; Sandra M. Sacco; Stephanie A. Schroer; Yujin E. Li; Helen Le; Wendy E. Ward; Minna Woo
• Keywords: Cathepsin K; Tartrate-resistant acid phosphatase; Cre recombinase; Bone remodeling

Osteoclasts are specialized cells of the hematopoietic lineage that responsible for bone resorption and play a critical role in musculoskeletal disease. JAK2 is key mediator cytokine growth factor signaling; however, its osteoclasts vivo has yet to be investigated. To elucidate osteoclasts, we generated an osteoclast-specific JAK2–KO (Oc-JAK2–KO) mouse using Cre/Lox-P system. Oc-JAK2–KO mice demonstrated marked postnatal restriction; this was not associated with significant changes density, microarchitecture, or strength, indicating observed phenotype due alterations canonical osteoclast function. Interestingly, had reduced expression IGF1, suggesting osteoclast-derived IGF1 determination body size. directly assess IGF1–KO mouse, which showed similar growth-restricted phenotype. Lastly, overexpression circulating by human transgene rescued defects mice, keeping causal these models. Together, our data show potentially novel Oc-JAK2 size, independent resorptive