| First Author | Zhang J | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 22 | Pages | e2220159120 |
| PubMed ID | 37216542 | Mgi Jnum | J:341016 |
| Mgi Id | MGI:7487938 | Doi | 10.1073/pnas.2220159120 |
| Citation | Zhang J, et al. (2023) Osteolectin increases bone elongation and body length by promoting growth plate chondrocyte proliferation. Proc Natl Acad Sci U S A 120(22):e2220159120 |
| abstractText | Osteolectin is a recently identified osteogenic growth factor that binds to Integrin alpha11 (encoded by Itga11), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While Osteolectin and Itga11 are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of Osteolectin associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that Osteolectin-deficient mice have shorter bones than those of sex-matched littermate controls. Integrin alpha11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin alpha11 as a regulator of bone elongation and body length in mice and humans. |
