UCLA

Bone health can be jeopardized by diseases such as osteoporosis, or by special environmental conditions like microgravity. Both conditions result in reduced bone mineral density (BMD) and an increased risk of bone fractures. NELL-1, a protein that binds integrin β1 and consequently induces Wnt/β-catenin, exhibits both bone-forming and anti-osteoclastic effects. Systemic delivery of NELL-1 via intravenous (IV) injections increases not only murine BMD and percent bone volume, but also new femoral bone formation. However, systemic delivery of NELL-1 under microgravity conditions in future spaceflight experimental studies would be more practical if it were accomplished through the intraperitoneal (IP) route. It is less technique sensitive, safer, and more patient friendly for eventual use by humans. The aim of this study was to experiment the intraperitoneal delivery of NELL-1 to reverse osteoporotic bone loss in mice under normal gravity conditions. First, a post-menopausal osteoporotic model (OVX) was successfully reproduced in BALB/c mice and a significant reduction in BMD was evident by DXA and microCT analyses. Second, two IP dosages of NELL-1 were injected into the OVX mice, resulting in reversed bone loss and positive gains in BMD and BV/TV. In conclusion, NELL-1 can be effectively delivered by systemic intraperitoneal injections to reverse osteoporotic bone loss and regulate bone homeostasis.