Inhibiting wear particles-induced osteolysis with doxycycline.
OBJECTIVE
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-kappaB ligand and the macrophage colony stimulating factor. DOX at a concentration of 5, 10, 15, and 20 microg/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 microg/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 x kg(-1) x 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.


CONCLUSIONS
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.
Zhang
Chao
C
Department of Orthopaedics, Ninth Peopleos Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Tang
Ting-Ting
TT
Ren
Wei-Ping
WP
Zhang
Xiao-Ling
XL
Dai
Ke-Rong
KR
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002470:Cell Survival / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000139:chemically induced / Q000517:prevention & control*; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry / Q000633:toxicity; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000633:toxicity; D011817:Rabbits; D000071681:Tartrate-Resistant Acid Phosphatase
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D019904:Polymethyl Methacrylate; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D004318:Doxycycline