| First Author | James AW | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7362 | PubMed ID | 26082355 |
| Mgi Jnum | J:223023 | Mgi Id | MGI:5646340 |
| Doi | 10.1038/ncomms8362 | Citation | James AW, et al. (2015) NELL-1 in the treatment of osteoporotic bone loss. Nat Commun 6:7362 |
| abstractText | NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin beta1 and consequently induces Wnt/beta-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss. |
