Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings.
BACKGROUND
The process of bone remodelling is disturbed in the development of osteoporosis.


OBJECTIVE
To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings.


METHODS
Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N(epsilon)-carboxymethyllysine.


RESULTS
Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs.


CONCLUSIONS
It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.
Hein
G
G
Department of Internal Medicine III, Rheumatology and Osteology, Friedrich-Schiller, University Jena, Germany. gert.hein@med.uni-jena.de
Weiss
C
C
Lehmann
G
G
Niwa
T
T
Stein
G
G
Franke
S
S
D000328:Adult; D000368:Aged; D001706:Biopsy; D016723:Bone Remodeling; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011499:Protein Processing, Post-Translational
D017127:Glycation End Products, Advanced; D007093:Imidazoles; C117197:imidazolone; C048496:N(6)-carboxymethyllysine; D008239:Lysine