Article

Particle-induced osteolysis in three-dimensional micro-computed tomography.

Department of Orthopedics, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Calcified Tissue International (Impact Factor: 2.5). 12/2007; 81(5):394-402. DOI: 10.1007/s00223-007-9077-2
Source: PubMed

ABSTRACT Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.

0 Bookmarks
 · 
125 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
    Biomaterials 01/2014; 35(22):5721–5730. · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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.
    Journal of Surgical Research 10/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 μM), as well as inducing apoptosis at higher dose (40 μM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.
    Breast Cancer Research and Treatment 01/2014; · 4.47 Impact Factor

Full-text (2 Sources)

View
40 Downloads
Available from
Jun 1, 2014