title: Histochemical evidence of zoledronate inhibiting c-src expression and interfering with CD44/OPN-mediated osteoclast adhesion in the tibiae of mice.
abstract: The purpose of this study was to investigate the effect of zoledronate (ZA) on osteoclast functions and viability in the tibiae of 8-week-old male mice. After weekly intravenous administration of ZA (125 μg/kg body weight) for 8 weeks, the mice were fixed by transcardial perfusion of 4% paraformaldehyde under anesthesia, and their tibiae were extracted for histochemical analysis. Compared with the control group, many tartrate-resistant acidic phosphatase-positive osteoclasts were found on the surface of the trabecular bone, but cartilage cores were obviously increased in the metaphysis of the ZA group. Osteoclasts of both groups showed similar expression of cathepsin K and matrix metalloproteinase-9. However, hardly any expression of c-src, a gene necessary for ruffled border formation and bone resorption, was found in osteoclasts of the ZA group. Moreover, no expression of CD44 or osteopontin (OPN) was observed in osteoclasts of the ZA group. Taken together, our findings suggest that ZA administration decreases the bone resorption ability of osteoclasts by inhibiting c-src expression and suppressing osteoclast adhesion by interfering with CD44/OPN binding.
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Bao
authors.initials: B
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.lastname: Yimin
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053495:Osteopontin / Q000378:metabolism*; D013977:Tibia / Q000166:cytology / Q000187:drug effects; D000077211:Zoledronic Acid; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D050071:Bone Density Conservation Agents; C476399:Cd44 protein, mouse; D004164:Diphosphonates; D018960:Hyaluronan Receptors; D007093:Imidazoles; C506896:Spp1 protein, mouse; D053495:Osteopontin; D000077211:Zoledronic Acid; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases