Miyata T, Iida Y, Notoya K, Taketomi S, Maeda K
Beta-2-microglobulin modified with advanced glycation end
products enhances osteoclast-induced bone resorption: Role
in the pathogenesis of dialysis-related amyloidosis
33rd Congress of the Eur Dial Transplant Assoc
Nephrol Dial Transplant
(Jun) 11:A240 1996
Advanced glycation end products (AGEs) are present in amyloid fibril
beta2-Microglobulin (beta2M) of patients with dialysis-related
amyloidosis (DRA), one of the characteristic features of which is an
accelerated bone resorption around amyloid deposits.
The aim
of the study was to investigate whether AGE-beta2M enhances
osteoclast-induced bone resorption by pit formation assay, using an
unfractionated bone cell culture system containing osteoclast and
osteoblasts from newborn mice. When the cells were cultured on dentin
slices, both AGE-beta2M purified from urine of long-term hemodialysis
patients and in-vitro prepared AGE-beta2M (beta2M incubated with
glucose for 60 days) increased the number of resorption pits formed by
osteoclasts, whereas normal beta2M did not enhance bone resorption.
AGE-beta2M, however, did not increase the number of tar/rate-resistant
acid phosphatase-positive cells, i.e., mature osteoclasts. Enhanced
bone resorption was also observed by AGE-BSA or when the cells were
cultured on AGE-modified dentin slices. AGE-induced bone resorption
was effectively inhibited by calcitonin and ipriflavone at the
therapeutic doses.
Comment: In conclusion, these data
suggest the AGEs enhance bone resorption, not by promoting
differentiation of osteoclast precursor cells into mature osteoclasts,
but by activating mature osteoclasts probably in concert with
osteoblasts. Thus, the bone resorption in dialysis related amyloid
might be the combined result of excessive accumulation of AGEs in
amyloid deposits linked to a heightened cellular (monocyte/macrophage
and osteoclast/osteoblast) response to these deposits (Carlo
Basile, M.D., Taranta, Italy).
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33rd Congress of the Eur Dial Transplant Assoc
CRF by organ system :
Joint disease, beta-2 microglobulin
CRF by problem area :
Bone disease/aluminum