Inflammatory Bone Loss Mediated by Specific Osteoclasts Precursors

Inflammatory bone loss (IBL) is discovered in many patients suffering from chronic inflammation diseases, such as rheumatoid arthritis, inflammatory bowel syndrome (IBD), cancer and more. The continuous immunological stimuli during those diseases result in hematopoiesis alterations and in specific, accumulation of undifferentiated heterogenous immature myeloid cells, or myeloid-derived suppressor cells (MDSCs), which induce vast immunosuppressive effects, including alterations of the bone formation-absorption homeostasis. Expressing similar markers, some MDSCs populations show great resemblance to osteoclasts precursors (OCPs).

We have identified two populations of OCPs with distinct responses to chronic inflammation – an inflammatory OCP subset (iOCPs) expands and is induced during chronic inflammation to become highly resorptive. In contrast, an abundant, second homeostatic OCP subset (hOCPs) was found to remain unchanged through the inflammation and even generated osteoclasts (OCs) with low activity in a chronic inflammation environment.

Due to OCP heterogeneity, it is still unknown whether a specific subset of OCPs forms highly active OCs, chronic inflammation effec on each of them, or what are the biological mechanisms found underlying those differences, therefore controlling resorption capacities of the OC formed by specific OCPs. On top of that, no such research has been conducted in humans up until now.

Our model suggests that the chronic inflammation suppressive environment induces iOCP-derived osteoclastogenesis, resulting in formation of excessively active OCs and finally, IBL. Nowadays, our objectives are to further investigate those OCP subsets - both on mice and human patients. Trying to find relevant biomarkers for early prediction and treatment of IBL.