Factors regulating bone remodeling processes in aseptic implant loosening

Hartmann, Eliza S.; Köhler, Miriam; Huber, Felicitas A.; Redeker, Julia I.; Schmitt, Bärbel; Schmitt‐Sody, Marcus; Summer, Burkhard; Fottner, Andreas; Jansson, Volkmar; Mayer-Wagner, Susanne

doi:10.1002/jor.23274

Cited by 17 publications

(21 citation statements)

References 45 publications

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“…It showed a more pro-osteoclastogenic environment in all transwell cultures, independent of cell type. These findings match our previous results, where periprosthetic tissue (from which PPFs were isolated) was analyzed [ 25 ]. The multilayer aggregates seem to present an interesting approach to analyze fibroblasts within a cell-culture system mimicking in vivo situations more closely.…”

Section: Discussionsupporting

confidence: 91%

“…There is lots of evidence that the function of fibroblast-like cells is far beyond creating a supporting tissue. Expression of RANKL, the final effector of osteoclastogenesis and bone resorption, has been shown to be increased in periprosthetic tissues [ 25 ]. It has been demonstrated that prostaglandin E2 (PGE2) signaling upregulates RANKL expression in PPFs [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…In multilayer cultures, a reduced OPG expression has been demonstrated for PPFs, SFs, and DFs. As periprosthetic tissues mostly are present with constantly very low OPG expression levels [ 25 , 27 , 28 ], it is of interest that an OPG reduction is obtained without the addition of further stimuli besides transwell culturing. We assume that OPG reduction, which is a pathomechanism in aseptic loosening, might be triggered by altered differentiation of fibroblast-like cells in transwell cultures [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures

et al. 2020

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Introduction Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures. Methods PPFs from periprosthetic tissues (n = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (n = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 103/cm2) or multilayer cultures (density 8.5 × 105/cm2) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR. Results Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased. Conclusion The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures

et al. 2020

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“…Wear debris particles typically stimulate osteoclast proliferation and differentiation by activating the OPG/RANKL/RANK pathway [ 30 ]. Hartmann et al [ 31 ] examined the mRNA expression of RANK and OPG and the binding activity of NF- κ B by coculturing titanium particles with IC-21 macrophages. The results showed that the osteolytic reaction process could be initiated by titanium particles through the OPG/RANKL/RANK pathway.…”

Section: Discussionmentioning

confidence: 99%

Micrometer-Sized Titanium Particles Induce Aseptic Loosening in Rabbit Knee

Guo

Gao

et al. 2018

BioMed Research International

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Wear debris induced aseptic loosening is the leading cause of total knee arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a major issue for introducing effective prevention and treatment methods, so a simplified yet efficient rabbit model was established to address this concern with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits were selected and divided into two groups (control = 10, study = 10). A TKA surgery was then performed for each of them, with implantation of a titanium rod prosthesis which was coated evenly with micrometer-sized titanium in the study group and nothing in the control group, into right femoral medullary cavity. After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining, Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting of some specific mRNAs and proteins in the interface membrane tissues around the prosthesis were carried out. The implantation of a titanium rod prosthesis coated with 20 μm titanium particles into the femoral medullary cavity of rabbits caused continuous titanium particle stimulation around the prosthesis, effectively inducing osteolysis and aseptic loosening. Titanium particle-induced macrophages produce multiple inflammatory factors able to activate osteoclast differentiation through the OPG/RANKL/RANK signaling pathway, resulting in osteolysis while suppressing the function of osteoblasts and reducing bone ingrowth around the prosthesis. This model simulated the implantation and loosening process of an artificial prosthesis, which is an ideal etiological model to study the aseptic prosthetic loosening.

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“…1 Successful bone remodeling in dental implants depends on the balanced activation of osteoclasts, which resorb the underlying bone tissue, followed by subsequent activation of osteoblasts, which are responsible for formation of new bone tissue in the peri-implant region. [2][3][4] Under osteoporotic conditions, estrogen deciency up-regulates osteoclastic activity, and this osteolysis phenomenon is further intensied. 5 Thereaer, it is desirable to nd useful interventions to promote the initial stability and long-term survival of implants, not only for the normal patients but also for the patients suffering from osteoporosis.…”

Section: Introductionmentioning

confidence: 99%