Harnessing the immune system to treat bone loss: The immunomodulatory and osteoprotective effects of the microalga Skeletonema costatum

The emerging field of osteoimmunology provides compelling evidence for the pivotal role of the immune system in the development of bone erosive pathologies such as osteoporosis. However, no immunomodulatory drug has yet been integrated into the therapeutic management of bone loss. Recently, driven by the demand for next-generation treatments for these conditions, natural compounds are gaining renewed attention as promising candidates for drug discovery.

In this study, we explored the anti-osteoclastogenic effects of an emerging extract from the marine microalga Skeletonema costatum . Using a zebrafish model of bone regeneration, we demonstrated the extract’s ability to inhibit the recruitment of osteoclast progenitors and block their differentiation into mature osteoclasts in vivo . Bulk RNA sequencing of early-stage fin blastemas revealed the downregulation of genes involved in inflammation, T-cell activation, and antigen presentation, suggesting that the extract exerts its effects primarily through immunomodulatory mechanisms. To further assess its therapeutic potential, we tested the extract in a medaka model of RANKL-induced osteoporosis and on a murine macrophage cell line. The extract effectively prevented bone loss in fish and inhibited osteoclastic differentiation in murine macrophages in vitro .

Collectively, our findings provide mechanistic insights into a novel, therapeutically relevant natural extract, offering proof of concept for its osteoprotective potential through immune system modulation.