Parthenolide inhibits polyethylene particle-induced mouse calvarial osteolysis in vivo.
BACKGROUND
Periprosthetic osteolysis and aseptic loosening (AL) after joint arthroplasty are serious problems encountered after an implant surgery. AL is possibly caused by osteolysis or local bone resorption induced by implant-derived wear particles. However, effective treatments for osteoclastic bone resorption and AL mediated by wear particles have not been developed except surgical revision. Therefore, a new strategy should be developed to improve osteolysis associated with AL via pharmacologic intervention.


METHODS
The effects of parthenolide (PTN), a nuclear factor-kappa B inhibitor and sesquiterpene lactone, on polyethylene particle-induced osteolysis in vivo were investigated using a mouse calvarial model. Bone volume/tissue volume (BV/TV, %), bone surface/bone volume (BS/BV, 1/mm), osteoclast number per bone perimeter (N.Oc/B.Pm, /mm), and eroded surface per bone surface (ES/BS, %) were determined by micro-computed tomography and histologic analyses.


RESULTS
Severe bone resorption and rapid osteoclast formation were found in the cranium of the subjects after polyethylene particles were implanted. ES/BS (P < 0.001), N.Oc/B.Pm (group III, P < 0.05; group IV, P < 0.001), and BS/BV (P < 0.001) increased compared with those in group II; BS/BV (P < 0.001) decreased in group II but was improved in groups III and IV, which were treated with PTN. No significant difference in these parameters was observed among groups I, III, and IV.


CONCLUSIONS
PTN possibly elicited therapeutic effects on osteolysis induced by wear particles, indicating that PTN could be used as a therapeutic agent of AL induced by wear particles.
Department of Orthopedics, Luohe Central Hospital, Luohe Medical College, Luohe, Henan province, People's Republic of China.
Yuwei
Y
Li
Department of Orthopedics, Kunhua Hospital, Kunming Medical College, Kunming, Yunnan province, People's Republic of China.
Chao
C
Zhang
Department of Orthopedics, Taizhou Central Hospital, Wenzhou Medical College, Taizhou, Zhejiang province, People's Republic of China. Electronic address: zhouxx1493@126.com.
Xiaoxiao
X
Zhou
Department of Orthopedics, Luohe Central Hospital, Luohe Medical College, Luohe, Henan province, People's Republic of China.
Haijiao
H
Wang
Department of Orthopedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Yuanqin
Y
Mao
Department of Orthopedics, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
Xiaoqing
X
Wang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004195:Disease Models, Animal; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010014:Osteolysis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D020959:Polyethylene / Q000633:toxicity*; D011475:Prosthesis Failure; D012717:Sesquiterpenes / Q000494:pharmacology*; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects*; D055114:X-Ray Microtomography
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes; C002669:parthenolide; D020959:Polyethylene
Calvarium; Micro-CT; Osteolysis; Parthenolide; Polyethylene particle