TY - JOUR
T1 - Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo
AU - Jiang, Xinyi
AU - Sato, Taishi
AU - Yao, Zhenyu
AU - Keeney, Michael
AU - Pajarinen, Jukka
AU - Lin, Tzu Hua
AU - Loi, Florence
AU - Egashira, Kensuke
AU - Goodman, Stuart
AU - Yang, Fan
N1 - Funding Information:
The authors would like to acknowledge National Institute of Health (grants 2R01AR055650 and 1R01AR063717) and Stanford Department of Orthopaedic Surgery for funding. X. Y. Jiang would like to thank Stanford Child Health Research Institute postdoctoral fellowship for support.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.
AB - Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.
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U2 - 10.1002/jor.22977
DO - 10.1002/jor.22977
M3 - Article
C2 - 26174978
AN - SCOPUS:84954077688
VL - 34
SP - 58
EP - 64
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 1
ER -