RANKL-associated suppression of particle-induced osteolysis in an aged model of Calcitonin and α-CGRP deficiency.
An aging population with higher bone turnover intensifies the need for joint replacement surgery. However, particle-induced osteolysis (PIO) remains a major cause of early implant loosening. Differences in bone remodeling between young and aged Calcitonin (CT)- and α-CGRP (Calcitonin gene-related peptide)-deficient mice (Calca(-/-)) might modify our previous findings regarding CT/α-CGRP in PIO. This may have important implications for PIO in an aging population. Four groups of twelve-month-old wild-type and Calca(-/-) mice underwent either SHAM surgery with and without CT, or polyethylene-particle implantation with related treatment. Morphometric changes were detected using μ-CT, histomorphometric analysis and by counting TRAP(+) cells (osteoclast-staining). Bone remodeling was assessed using serum and urinary markers. There was no osteolysis in aged particle-treated Calca(-/-) animals and the effect of CT on PIO was reduced compared to wild-type mice. However, there were significantly higher numbers of TRAP(+) cells in Calca(-/-) animals, and bone remodeling markers revealed a significant increase in OPG/OCN and a significant reduction in RANKL compared to aged wild-type mice. CT/α-CGRP modulates bone cell activity in PIO in aged mice in a way that is distinct from young animals. This may have implications for the treatment of PIO in the periprosthetic surface of joint replacements in an aging population.
Department of Trauma Surgery, University of Duisburg-Essen, Essen, Germany.
Max D
MD
Kauther
Carl
C
Neuerburg
Florian
F
Wefelnberg
Hagen S
HS
Bachmann
Rüdiger
R
Schlepper
Gero
G
Hilken
Martina
M
Broecker-Preuss
Florian
F
Grabellus
Arndt F
AF
Schilling
Marcus
M
Jäger
Christian
C
Wedemeyer
D000818:Animals; D016723:Bone Remodeling; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D004195:Disease Models, Animal; D051379:Mice; D010014:Osteolysis; D053245:RANK Ligand / Q000502:physiology*
D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide