ADVANCED GLYCATION END-PRODUCTS ENHANCE OSTEOCLAST-INDUCED BONE-RESORPTION IN CULTURED MOUSE UNFRACTIONATED BONE-CELLS AND IN RATS IMPLANTED SUBCUTANEOUSLY WITH DEVITALIZED BONE PARTICLES
T. Miyata et al., ADVANCED GLYCATION END-PRODUCTS ENHANCE OSTEOCLAST-INDUCED BONE-RESORPTION IN CULTURED MOUSE UNFRACTIONATED BONE-CELLS AND IN RATS IMPLANTED SUBCUTANEOUSLY WITH DEVITALIZED BONE PARTICLES, Journal of the American Society of Nephrology, 8(2), 1997, pp. 260-270
Advanced glycation end products (AGE) are formed in long-lived matrix
proteins by a nonenzymatic reaction with sugar. The presence of AGE in
beta(2)-microglobulin-amyloid fibrils of dialysis-related amyloidosis
, one of the characteristic features of which is an accelerated bone r
esorption around amyloid deposits, was recently demonstrated. This sug
gested a potential link of AGE in bone resorption and initiated this i
nvestigation of whether AGE enhance bone resorption. When mouse unfrac
tionated bone cells containing osteoclasts were cultured on dentin sli
ces, both AGE-modified beta(2)-microglobulin and BSA increased the num
ber of resorption pits formed by osteoclasts, whereas their normal cou
nterparts or those modified with the early glycation products did not.
AGE proteins, however, did not increase the number of newly formed os
teoclasts, even in the coculture of mouse bone marrow cells with osteo
blastic cells isolated from mouse calvaria. Enhanced bone resorption w
as also observed when unfractionated bone cells were cultured on AGE-m
odified dentin slices. AGE-enhanced bone resorption was effectively in
hibited by calcitonin and ipriflavone, both of which are inhibitors of
bone resorption. AGE-enhanced bone resorption was further supported b
y in vivo evidence that rat bone particles-upon incubation with glucos
e for 60 days (AGE-bone particles)-when implanted subcutaneously in ra
ts, were resorbed to a much greater extent than control bone particles
upon parallel incubation without glucose. These findings suggest that
AGE enhance osteoclast-induced bone resorption. Although the mechanis
m remains unknown, AGE are unlikely to promote differentiation of oste
oclast progenitors into osteoclasts, suggesting that AGE activate oste
oclasts or alter microenvironments favorable for bone resorption by os
teoclasts. The modification of bone matrices with AGE might play a rol
e in the remodeling of senescent cent bone matrix tissues, further imp
licating a pathological significance of AGE in dialysis-related amyloi
dosis or osteoporosis associated with diabetes and aging.