Multiple functions of osteoclasts and potential usefulness of phosphatidylserine-containing liposomes on bone diseases

Osteoclasts (OCs) are well known as the bone resorption cells in normal bone remodeling and pathological bone loss by increasing their number and resorptive activity. They are derived from myeloid osteoclast precursors (OPs) under the influence of the surrounding cells. There is growing evidence that OCs have multiple functions besides bone resorption. OCs secrete mediators to work as functional antigen-presenting cells in immune responses, affect angiogenesis by regulating the function of capillaries' endothelial cells, and regulate hematopoietic stem cell (HSCs) functions. Furthermore, OCs can phagocytoze apoptotic bone cells. Phagocytosis of apoptotic cells causes phagocytes to secrete anti-inflammatory mediators to control their functions in autocrine and paracrine manners. Posphatidylserine-containing liposomes (PSLs) are known to mimic the effects of apoptotic cells on phagocytes. We have found that phagocytosis of PSLs by OPs can regulate their secretion of anti-inflammatory mediators, including prostaglandin E₂ and transforming growth factor-β1, to inhibit OCs formation and inflammatory bone loss. In addition, PSLs promote the maturation of osteoblasts. Therefore, PSLs may provide potential pharmacological interventions against bone diseases through the regulation of these multiple functions of OCs.