Mechanical instability induces osteoclast differentiation independent of the presence of a fibrous tissue interface and osteocyte apoptosis in a rat model for aseptic loosening

Madsen, R.; Nam, Denis; Schilcher, Jörg; Dvorzhinskiy, Aleksey; Sutherland, J; Bostrom, F Mathias; Fahlgren, Anna

doi:10.1080/17453674.2019.1695351

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…29 However, using a model of instability-induced loosening, osteoclast differentiation was found to be independent of osteocyte apoptosis. 18 In this study, there was a large…”

Section: Discussionmentioning

confidence: 89%

“…The fibrous tissue layer is thought to be the result of the loosening process rather than the cause. 14,18 In the metaphysis, the interdigitated trabecular bone was not viable, but also did not resorb with time. There was early formation of bone around the cement border in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer.…”

Section: Discussionmentioning

confidence: 99%

“…25,32 In this scenario, fluid flow in narrow gaps is caused by local micromotion, resulting in supraphysiologic fluid flow and pressure. 33 Supraphysiologic flow induces pro-osteoclastic signaling 34 and osteoclast differentiation is induced by mechanical instability, 18 resulting in increased focal bone resorption. 35 The local flow environment found in human knee arthroplasty appears to be similar to that found in the rat hemiarthroplasty model in terms of magnitude of fluid shear stress, suggesting that any response due to mechanical instability on the local cellular environment would be similar.…”

Section: Discussionmentioning

confidence: 99%

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Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Mann

Miller

Rossow

et al. 2021

Journal Orthopaedic Research

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Aseptic loosening of total knee arthroplasty continues to be a challenging clinical problem. The progression of the loosening process, from the initial well-fixed component, is not fully understood. In this study, loss of fixation of cemented hemiarthroplasty was explored using 9-month-old Sprague-Dawley rats with 0, 2, 6, 12, 26 week end points. Morphological and cellular changes of cement-bone fixation were determined for regions directly below the tibial tray (epiphysis) and distal to the tray (metaphysis). Loss of fixation, with a progressive increase in cement-bone gap volume was found in the epiphysis (0.162 mm 3 /week), but did not progress appreciably in the metaphysis (0.007 mm 3 /week). In the epiphysis, there was an early and sustained elevation of osteoclasts adjacent to the cement border and development of a fibrous tissue layer between the cement and bone. There was early formation of bone around the cement in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer. Implant positioning was also an important factor in the cement-bone gap formation, with greater gap formation for implants that were placed medially on the tibial articular surface. Loss of fixation in the rat model mimicked patterns found in human arthroplasty where cement-bone gaps initiate under the tibial tray, at the periphery of the implant. This preclinical model could be used to study early biological response to cemented fixation and associated contributions of mechanical instability, component alignment, and periprosthetic inflammation.

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“…29 However, using a model of instability-induced loosening, osteoclast differentiation was found to be independent of osteocyte apoptosis. 18 In this study, there was a large…”

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Mann

Miller

Rossow

et al. 2021

Journal Orthopaedic Research

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“…When bone defect reaches a certain volume, it is difficult to complete bone-defect healing by its regeneration ability, especially combined with osteoporosis characterized by markedly impaired bone-repair ability [ 5 , 6 ]. Over the last few decades, bone-substitute materials have received significant attention, and numerous bone biomaterials researches have been reported [ 7 , 8 ]. While autologous bone graft is still considered to be the “Gold Standard” for bone-defect reconstruction, the complications such as extension of surgical time, increase of surgical sites, and infection chance and aggravation of patient pain may therefore promote people to find and design new alternative drugs and biological materials [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Tao

et al. 2021

J Mater Sci: Mater Med

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The purpose was to observe whether valproic acid (VPA) has a positive effect on bone-defect repair via activating the Notch signaling pathway in an OVX rat model. The MC3T3-E1 cells were cocultured with VPA and induced to osteogenesis, and the osteogenic activity was observed by alkaline phosphatase (ALP) staining, Alizarin Red (RES) staining and Western blotting (WB). Then the hydrogel-containing VPA was implanted into the femoral epiphysis bone-defect model of ovariectomized (OVX) rats for 12 weeks. Micro-CT, biomechanical testing, histology, immunofluorescence, RT-qPCR, and WB analysis were used to observe the therapeutic effect and explore the possible mechanism. ALP and ARS staining and WB results show that the cell mineralization, osteogenic activity, and protein expression of ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, and JAG1 of VPA group is significantly higher than the control group. Micro-CT, biomechanical testing, histology, immunofluorescence, and RT-qPCR evaluation show that group VPA presented the stronger effect on bone strength, bone regeneration, bone mineralization, higher expression of VEGFA, BMP-2, ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, and JAG1 of VPA when compared with OVX group. Our current study demonstrated that local treatment with VPA could stimulate repair of femoral condyle defects, and these effects may be achieved by activating Notch signaling pathway and acceleration of blood vessel and bone formation.

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“…In recent years, the failure rates of orthopedic titanium implant have rapidly increased, but the loss of bone mass around prostheses is the critical reason for implant failure, as it causes initial instability and aseptic loosening, especially in osteoporosis patients. 5,29 Despite great advances in materials science and surgical techniques, as clinicians, we are still faced with an aging population that sustains costly osteoporotic fractures. Unfortunately, there is no good solution for protecting bone mass around orthopedic titanium implant in osteoporosis patients.…”

Section: Discussionmentioning

confidence: 99%

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

Tao

Yang

2021

J Biomater Appl

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Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.

show abstract

Mechanical instability induces osteoclast differentiation independent of the presence of a fibrous tissue interface and osteocyte apoptosis in a rat model for aseptic loosening

Cited by 7 publications

References 24 publications

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

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