Plasmalemmal interface for calcium signaling in osteoclast differentiation

There are three hot topics for research on calcium (Ca) signaling in osteoclast differentiation. First, Transient receptor potential (TRP) vanilloid channel 4 is important for late differentiation. In addition, TRP canonical channels and Ca release-activated Ca channels cooperatively inhibit differentiation. Second, antioxidants against reactive oxygen species inhibit osteoclastogenesis and bone loss. Mechanical stress in osteoclasts is also a focus of investigation. Third, immunoreceptor tyrosine-based activation motif (ITAM) adaptor-receptor complexes evoke costimulatory signals for osteoclastogenesis. ITAM molecules like cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) for Fc receptor gamma and Siglec-15 for DNAX-activating protein of 12 kD (DAP12) are potential targets for modification in osteoclast inhibition. Detection and analysis methods need to be objective and interdisciplinary to clarify the integrative mechanism for Ca oscillations induced by many factors including Ca channels and transporters.