Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells

Vallés, Gema; Pérez, Concepción; Boré, Alba; Martín-Saavedra, Francisco M.; Saldaña, Laura; Vilaboa, Nuria

doi:10.1016/j.actbio.2012.08.027

Cited by 18 publications

(25 citation statements)

References 45 publications

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“…Statins affect the mevalonate pathway producing farnesyl- and geranylgeranyl pyrophosphates, which post-translationally modulate bone metabolism regulating small G proteins. Additionally, this could be associated with attenuation of the particle-induced activation of monocytes and/or production of IL-6 [165, 166]. Finally, anabolic steroids have positive effects on the musculoskeletal system, therefore, some investigators have used them in order to increase the muscle size and strength and diminish early bone resorption [167].…”

Section: Clinical Impact Of Research On Periprosthetic Osteolysismentioning

confidence: 99%

Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms

et al. 2013

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Aseptic loosening and other wear-related complications are one of the most frequent late reasons for revision of total knee arthroplasty (TKA). Periprosthetic osteolysis (PPOL) predates aseptic loosening in many cases indicating the clinical significance of this pathogenic mechanism. A variety of implant-, surgery-, and host-related factors have been delineated to explain the development of PPOL. These factors influence the development of PPOL due to changes in mechanical stresses within the vicinity of the prosthetic device, excessive wear of the polyethylene liner, and joint fluid pressure and flow acting on the peri-implant bone. The process of aseptic loosening is initially governed by factors such as implant/limb alignment, device fixation quality, and muscle coordination/strength. Later large numbers of wear particles detached from TKAs trigger and perpetuate particle disease, as highlighted by progressive growth of inflammatory/granulomatous tissue around the joint cavity. An increased accumulation of osteoclasts at the bone-implant interface, an impairment of osteoblast function, mechanical stresses, and an increased production of joint fluid contribute to bone resorption and subsequent loosening of the implant. In addition, hypersensitivity and adverse reactions to metal debris may contribute to aseptic TKA failure but should be determined more precisely. Patient activity level appears to be the most important factor when the long-term development of PPOL is considered. Surgical technique, implant design, and material factors are the most important preventative factors because they influence both the generation of wear debris and excessive mechanical stresses. New generations of bearing surfaces and designs for TKA should carefully address these important issues in extensive preclinical studies. Currently, there is little evidence that PPOL can be prevented with pharmacological interventions.

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Section: Clinical Impact Of Research On Periprosthetic Osteolysismentioning

confidence: 99%

Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms

et al. 2013

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“…Despite the great variability found in particle size, most Ti and PE particles used in vitro had diameters of 4–4.5 µm [31,33,38,42,49] and 1.7 µm [20,43,48], respectively, with dimensions never exceeding 10 µm. In regards to in vivo models, Ti ranged from 0.1 to 20 µm [55,57,59,60], while PE particles dimensions were usually about 7 µm [61,62,63].…”

Section: Discussionmentioning

confidence: 99%

“…Mouse macrophage cell lines (RAW264.7) were the most used [4,6,27,28,29,30,31,32,33,34,35,36,37], followed by OB precursors derived from mouse calvaria (MC3T3-E1) [27,28,38,39,40,41] and human (Saos-2 and MG-63) [1,42,43] or rat (ROS 17/2.8) [44] osteosarcoma and monocitic (THP-1) [20,45,46] cell lines. In addition, other studies also used primary cells: mouse [28,47] or human [42,48] OBs, mouse or rat bone-marrow-derived macrophages (BMM) [28,49,50,51], human MSCs [39,52], mouse [47] or human [53] FBs and mouse peritoneal macrophages [54]. In one study, mouse calvaria [4] were cultured in toto.…”

Section: Gene Expression In Osteolysismentioning

confidence: 99%

“…In one study, mouse calvaria [4] were cultured in toto. Regarding the different wear particles used, Ti [4,6,27,28,29,30,31,32,33,38,39,42,45,50,52,53] was the most employed, followed by PE [20,34,37,43,47,48], PMMA [36,41,51] and Co-Cr alloy [1,40,46]. Three studies compared Ti effects with PMMA [49], zirconia (ZrO 2 ) [54] and aluminia ceramic (CE) [34] and one compared PE and hydroxyapatite (HA) particles [44].…”

Section: Gene Expression In Osteolysismentioning

confidence: 99%

“…In cells of the osteoblastic lineage, Ti particles induced an increase in the pro-inflammatory genes and a decrease in Osteoprotegerin (OPG) gene observed in macrophagic cells and in CB2 [27,28,38,39,42]. In addition, one study analyzed osteogenesis and apoptotic pathways with microarray in hMSCs, showing an up-regulation of genes of pro-apoptotic proteins (Bcl-2-associated death promoter (BAD), Cluster of Differentiation 70 (CD70), B-cell lymphoma 2 (BCL2) and a down-regulation of anti-apoptotic and osteogenesis genes, encoding for Cartilage oligomeric matrix protein (COMP), Fibroblast Growth Factor Receptor 2 (FGFR2), Insulin-like growth factor 1 (IGF-1), Bone morphogenetic protein 6 (BMP6), Collagens (COLLs), (sex determining region Y)-box 9 (SOX9) and OPG [52].…”

Section: Gene Expression In Osteolysismentioning

confidence: 99%

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Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies

Veronesi

Tschon

Fini

2017

IJMS

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Aseptic loosening (AL) due to osteolysis is the primary cause of joint prosthesis failure. Currently, a second surgery is still the only available treatment for AL, with its associated drawbacks. The present review aims at identifying genes whose expression is altered in osteolysis, and that could be the target of new pharmacological treatments, with the goal of replacing surgery. This review also aims at identifying the molecular pathways altered by different wear particles. We reviewed preclinical and clinical studies from 2010 to 2016, analyzing gene expression of tissues or cells affected by osteolysis. A total of 32 in vitro, 16 in vivo and six clinical studies were included. These studies revealed that genes belonging to both inflammation and osteoclastogenesis pathways are mainly involved in osteolysis. More precisely, an increase in genes encoding for the following factors were observed: Interleukins 6 and 1β (IL16 and β), Tumor Necrosis Factor α (TNFα), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acid phosphatase (TRAP). Titanium (Ti) and Polyethylene (PE) were the most studied particles, showing that Ti up-regulated inflammation and osteoclastogenesis related genes, while PE up-regulated primarily osteoclastogenesis related genes.

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p38 signaling in titanium particle‐induced MMP‐2 secretion and activation in differentiating MC3T3‐E1 cells

Chen

Dong

et al. 2013

J Biomedical Materials Res

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The periprosthetic osteolysis induced by wear particles contributes to aseptic loosening after joint arthroplasty. The molecular mechanism underlying osteolysis remains to be described. In this study, cultured MC3T3-E1 cells were incubated with titanium particles. We investigated the role of p38 mitogen-activated protein kinase in the expression of MMP-2 in response to wear particles. Our results demonstrated MC3T3-E1 cells exposed to titanium particles had significantly increased levels of MMP-2 and MT1-MMP mRNA, whereas the TIMP-2 mRNA level was unchanged. In MC3T3-E1 cells, the protein expression of MMP-2, MT1-MMP, and active p38 was also elevated after titanium particle exposure, as detected by Western blot and Biotrak activity analyses. Inhibition studies showed that the specific p38 inhibitor SB203580 completely abrogated the increase in MMP-2 and MT1-MMP production induced by the titanium particles. Moreover, our results revealed that conditioned media-stimulated osteoclast formation was related to the MMP-2 activity of osteoblasts that were challenged with Ti particles. This study demonstrated that p38 signaling is required for MMP-2 activity in osteoblasts under wear particle-induced conditions. MMP-2 could act as a catabolic element or a proinflammatory factor contributing to periprosthetic osteolysis. Therefore, the p38 pathway and MMP-2 may play a critical role in the development of aseptic loosening.

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Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells

Cited by 18 publications

References 45 publications

Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms

Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms

Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies

p38 signaling in titanium particle‐induced MMP‐2 secretion and activation in differentiating MC3T3‐E1 cells

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