Open AccessInhibiting wear particles‐induced osteolysis with doxycycline
Author(s) -
ZHANG Chao,
TANG Tingting,
REN Weiping,
ZHANG Xiaoling,
DAI Kerong
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00638.x
Subject(s) - osteolysis , tartrate resistant acid phosphatase , osteoclast , bone resorption , chemistry , resorption , in vivo , rankl , acid phosphatase , macrophage colony stimulating factor , bone marrow , macrophage , microbiology and biotechnology , in vitro , medicine , activator (genetics) , biochemistry , receptor , dentistry , biology , enzyme
Aim: To study the effect of doxycycline (DOX) on osteoclastogenesis, mature osteoclast fate and function, wear particles‐induced osteoeolysis, and to provide some foundation for treating aseptic loosening and osteolysis after joint arthroplasty. Methods: Osteoclasts were generated from mouse bone marrow monocytes with the receptor activator of NF‐κB ligand and the macrophage colony stimulating factor. DOX at a concentration of 5, 10, 15, and 20 μg/mL was respectively added to the medium. Seven days later, the osteoclasts were determined through tartrate‐resistant acid phosphatase (TRAP) staining. Mature osteoclasts were isolated from newborn rabbits and cultured for 3 d in 24‐well plates or on bone slices. DOX at a concentration of 5, 10, 15, and 20 μg/mL was respectively added to the medium. After TRAP staining, the osteoclasts were counted, resorption on bone slices was quantified, and the area was calculated after toluidine blue and Mayer‐hematoxylin staining. Polymethyl methacrylate (PMMA) or ultra‐high molecular weight polyethylene (UHMWPE) particles were implanted on the calvariae of C57BL/J6 mice. DOX, at a dose of 2 and 10 mg·kg −1 ·d −1 , was respectively given intraperitoneally for 7 d. Seven days later, the calvariae were removed and processed for pathological analysis. Results: DOX treatment effectively inhibited in vitro osteoclastogenesis, affected the fate of mature osteoclasts, and inhibited mature osteoclasts, causing bone resorption. In vivo data indicated that DOX strongly inhibited PMMA or UHMWPE‐induced osteolysis and osteoclastogenesis. Conclusion: DOX can effectively inhibit osteoclastogenesis and affect mature osteoclast fate and suppress wear particles induced by osteolysis and osteoclastogenesis. DOX might be useful in the treatment or prevention of wear particles‐induced osteolysis and aseptic loosening for its effect on osteoclast generation and mature osteoclast fate and function.