Osteopetroses and immunodeficiencies in humans

Area of Science:

• Immunology
• Bone Biology
• Pathology

Background:

• Osteoclasts and immune cells play critical roles in human and murine pathologies.
• Their interactions have led to the discovery of shared pathways and novel molecular mechanisms.

Purpose of the Study:

• To review pathologies involving both osteoclasts and immune cells.
• To highlight the discovery of novel interactions and shared pathways between these cell types.

Main Methods:

• Review of murine models with gene targeting of key molecules in osteoclast differentiation.
• Analysis of receptor activator of nuclear factor kappa-B ligand (RANKL) and its role in autoimmune diseases.
• Identification of immunoreceptor tyrosine-based activation motif receptors and adaptors linking immunity and bone.

Main Results:

• Murine models deficient in RANKL, RANK, and TNFR-associated factor 6 showed abnormalities in bone resorption and immune function.
• Lymphocyte-secreted RANKL stimulates osteoclasts in autoimmune diseases like rheumatoid arthritis.
• Osteoclast function is linked to innate and adaptive immunity via specific receptors and adaptors.
• Osteoclasts are crucial for hematopoietic stem-cell mobilization, regulating lymphoid cells.

Conclusions:

• The study establishes osteoimmunology as a new research field.
• Unsuspected links between bone remodeling and immune response are being uncovered.
• These findings have significant implications for understanding and treating diseases involving bone and immunity.