Is there another possible approach to inhibit wear particles-induced inflammatory osteolysis?
Periprosthetic osteolysis can lead to aseptic loosening of components, massive bone loss that renders revision surgery substantially more complex. Recent researches had been demonstrated the biological cascade of events that was initiated by particulate debris and involved in proinflammatory cytokine production and osteoclastogenesis, finally resulted in periprosthetic bone loss. Recent advances in our understanding of cellular and molecular mechanisms of periprosthetic bone loss had highlighted cytokine release and osteoclasts function controlled by numerous intracellular signaling pathway, one of which was TNF-like weak inducer of apoptosis (TWEAK) binding FGF-inducible molecule 14 (Fn14). TWEAK and/or Fn14 inhibition can diminish joint inflammation, synovial angiogenesis, as well as cartilage and bone erosion. At present there were no approved nonoperative treatments for periprosthetic osteolysis. Specific inhibition or blockade of signaling pathway, however, may be one of potential methods to treat periprosthetic osteolysis. As the implant interface cells were located in the closed joint space, intra-articular injection of some proteins or antibodies to block TWEAK/Fn14 signaling pathway was accessible as local administration to avoid systemic side effect. We hypothesized that local administration of some proteins or antibodies to block TWEAK/Fn14 signaling pathway could inhibit wear particles-induced inflammatory osteolysis. In our opinion, specific signaling pathway blockage may be with promising future prospects for effective therapeutic interventions in humans.
Department of Orthopedics, Tongji Hospital, Tongji University, Shanghai, PR China.
Yu-Ping
YP
Liu
Guang-Rong
GR
Yu
Ke
K
Li
Feng
F
Yuan
D016475:3T3 Cells; D000818:Animals; D019643:Arthroplasty, Replacement; D001842:Bone and Bones / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007270:Injections, Intra-Articular; D007595:Joint Prosthesis; D051379:Mice; D008954:Models, Biological; D010010:Osteoclasts / Q000378:metabolism; D010014:Osteolysis / Q000175:diagnosis* / Q000517:prevention & control*; D011475:Prosthesis Failure; D015398:Signal Transduction; D048069:Tumor Necrosis Factors / Q000378:metabolism
D000074049:Cytokine TWEAK; D016207:Cytokines; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors