Subject: Inflammatory bone destruction and osteoimmunology
Volume 40 Issue 4 Page 287 - August 2005
Mini review
Inflammatory bone destruction and osteoimmunology
Hiroshi Takayanagi
Objectives: The metabolism of hard tissue is influenced by
the immune
system. Research into the bone destruction associated with
inflammatory diseases such as periodontal disease and rheumatoid
arthritis has highlighted the importance of the interplay of
the
immune and skeletal systems. This interdisciplinary research
field,
called 'osteoimmunology', has become increasingly important
for each
system by itself as well as the biology linking them. The history
and
recent progress of this field are reviewed.
Material and methods: 'Osteoimmunology' was coined to describe
the
pioneering work on the T-cell regulation of osteoclastogenesis
by the
receptor activator of nuclear factor-B ligand (RANKL) and interferon
(IFN)-. Accumulating evidence suggests that the immune and
skeletal
systems share not only cytokines but also various signaling
molecules, transcription factors and membrane receptors. The
contribution of T cells to the pathogenesis of inflammatory
bone
destruction is discussed, and our recent findings are summarized
to
illustrate how the osteoimmunological network functions.
Results: RANKL is an osteoclastogenic cytokine that links bone
and
the immune system. Immunomodulatory cytokines such as IFNs
also
participate in the regulation of RANKL signaling and inflammatory
bone loss. The transcription factor nuclear factor of activated
T
cells c1 (NFATc1) has been identified as a master switch regulator
of
osteoclastogenesis. In addition, immunoglobulin-like receptors
are
critically involved in bone homeostasis.
Conclusion: Bone turns out to be a dynamic tissue that is constantly
renewed, where the immune system participates to a hitherto
unexpected extent. This emerging field will be of great importance
to
a better understanding and treatment of diseases of the skeletal
and
immune systems, as well as to the fundamental biology underpinning
both.
