The Experts below are selected from a list of 4905 Experts worldwide ranked by ideXlab platform
Jianning Zhao - One of the best experts on this subject based on the ideXlab platform.
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the metal nanoparticle induced inflammatory response is regulated by sirt1 through nf κb deacetylation in aseptic Loosening
International Journal of Nanomedicine, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Qian Gao, Jianning ZhaoAbstract:Aseptic Loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic Loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic Loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of Prosthesis Loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening.
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sirt1 protects osteoblasts against particle induced inflammatory responses and apoptosis in aseptic Prosthesis Loosening
Acta Biomaterialia, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Nirong Bao, Qian Gao, Jianning ZhaoAbstract:Abstract We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic Loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic Prosthesis Loosening. Statement of Significance Aseptic Loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic Loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic Loosening and further investigated the underlying mechanism of aseptic Loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.
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progress on the relationship between wear debris induced apoptosis and aseptic Loosening of Prosthesis
China Journal of Orthopaedics and Traumatology, 2013Co-Authors: Guoyin Liu, Jianning Zhao, Rui WangAbstract:Aseptic Looseningis is one of the most frequent long-term complications after joint replacement, which limits the service lire of Prosthesis. A lot of studies have been focused on macrophage, osteoblast, osteoclast and fibroblast in interface membranes around prostheses recently. Aseptic Loosening of orthopedic implants used in joint replacement results from bone loss that occurs through the resorptive activity of inflammatory cells activated by the presence of wear particles. Apoptosis has been observed in the periprosthetic site and it has been interpreted as a sign of resolution of inflammation suggesting that apoptosis-related events are indeed associated with periprosthetic osteolysis,targeting the Apoptosis pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening. In this thesis,the relationship between wear debris-induced apoptosis and aseptic Loosening of prostheses are expounded in detail.
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particle induced osteolysis mediated by endoplasmic reticulum stress in Prosthesis Loosening
Biomaterials, 2013Co-Authors: Rui Wang, Zhenheng Wang, Guoyin Liu, Hao Shi, Jiangning Chen, Lei Dong, Jianning Zhao, Junfeng ZhangAbstract:We hypothesized that endoplasmic reticulum (ER) stress in macrophages induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total hip arthroplasty (THA) failure. In the present study, the expression of ER stress markers was examined by Western blot in macrophages treated with particles from materials used in prosthetics, specimens from PIO animal models and patients suffering from aseptic Loosening. To address whether ER stress triggers these inflammatory responses, the effect of an ER stress blocker on the expression of inflammatory cytokines in particle-treated macrophages and PIO animal models was tested. The results demonstrated that ER stress markers were significantly upregulated in particle-treated macrophages, periosteum tissues from PIO animal models and clinical specimens of Prosthesis Loosening. Blocking ER stress with a specific inhibitor dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and in vivo. Furthermore, in PIO animal models, this ER stress blocker dramatically suppressed the differentiation of osteoclasts and reduced the severity of osteolysis. Thus, the results of the present study suggest that ER stress plays a key role in particle-induced osteolysis and that targeting the ER stress pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening.
L Pimenta - One of the best experts on this subject based on the ideXlab platform.
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porous coated motion cervical disc replacement a biomechanical histomorphometric and biologic wear analysis in a caprine model
Spine, 2006Co-Authors: N. Hu, J C Sefter, Paul C Mcafee, Andy Cappuccino, L PimentaAbstract:STUDY DESIGN: The biomechanical, histopathologic, and histomorphometric characteristics of cervical disc replacement were assessed in a caprine animal model. OBJECTIVE: To investigate the biomechanical, porous ingrowth, and histopathologic characteristics of the Porous Coated Motion (PCM) Cervical Disc replacement (Cervitech, Inc., Rockaway, NJ). SUMMARY OF BACKGROUND DATA: As an alternative to anterior cervical interbody arthrodesis, an artificial cervical disc serves to replace the symptomatic degenerated disc, restore the functional biomechanical properties of the motion segment, and preserve neurologic function. METHODS: There were 12 mature Nubian goats divided into 2 groups based on postoperative survival periods of 6 (n = 6) and 12 months (n = 6). Using an anterior surgical approach, a complete discectomy was performed at the C3-C4, followed by implantation of the PCM device. Functional outcomes of the disc Prosthesis were based on computerized tomography (CT), multidirectional flexibility testing, undecalcified histology, histomorphometric, and immunocytochemical analyses. RESULTS: There was no evidence of Prosthesis Loosening, or neurologic or vascular complications. CT showed the ability to image and assess the cervical spinal canal for the presence of compressive pathology in the area of the CoCrMo Prosthesis. Multidirectional flexibility testing under axial rotation and lateral bending indicated no differences in the full range of intervertebral motion between the disc Prosthesis and nonoperative controls (P > 0.05). Based on immunohistochemical and histologic analysis, there was no evidence of particulate debris, cytokines, or cellular apoptosis within the local or systemic tissues. Moreover, review of the spinal cord at the operative levels indicated no evidence of cord lesions, inflammatory reaction, wear particles, or significant pathologic changes in any treatment. Histomorphometric analysis at the metal-bone interface indicated the mean trabecular ingrowth of 40.5% +/- 24.4% and 58.65% +/- 28.04% for the 6 and 12-month treatments, respectively. CONCLUSION: To our knowledge, this serves as the first in vivo time-course study investigating the use of the PCM device for cervical arthroplasty. All 12 animals undergoing cervical disc replacement had no evidence of implant Loosening, subluxation, or inflammatory reactions. PCM cervical arthroplasty permits unobstructed visualization of the spinal canal based on CT imaging. Segmental intervertebral motion was preserved under axial rotation and lateral bending loading conditions, while at the same time permitting porous osseointegration at the Prosthesis-bone interface. Based on histopathologic review of all local and systemic tissues, there was no evidence of particulate wear debris, cytokines, cellular apoptosis, or significant pathologic changes in any treatment.
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porous coated motion cervical disk replacement a biomechanical histomorphometric and biologic wear analysis in a caprine model
Orthopaedic Proceedings, 2005Co-Authors: B W Cunningham, J C Sefter, L Pimenta, Andy Cappuccino, N. Hu, Paul C McafeeAbstract:Introduction The current study was undertaken to investigate the biomechanical and biologic in-growth characteristics of the Porous Coated Motion™ cervical disc Prosthesis following a six and twelve-month implant duration using an in-vivo caprine model. Methods Twelve mature Nubian goats were divided into two groups based on post-operative survival periods of six (n=6) and twelve months (n=6). Using an anterior surgical approach, a complete diskectomy was performed at the C3-C4, followed by implantation of the Porous Coated Motion™ device. Functional outcomes of the disc Prosthesis were based on computed tomography (CT), multi-directional flexibility testing, undecalcifed histology, histomorphometry and immunocytochemical analyses. Results There was no evidence of Prosthesis Loosening, neurologic or vascular complications. CT scans demonstrated the ability to image and assess the cervical spinal canal for the presence of compressive pathology in the area of the CoCrMo Prosthesis. Multi-directional flexibility testing indicated no differences in full range of intervertebral motion between the disc Prosthesis and non-operative controls (n=7) under axial rotation or lateral bending conditions (p>0.05). Flexion-extension produced significantly more motion for the intact spine compared to the cervical disc Prosthesis (p Discussion All twelve goats undergoing cervical disc replacement had no evidence of implant Loosening or inflammatory reactions from particulate wear debris. Segmental intervertebral motion was preserved based on multi-directional flexibility testing. The TiCaP porous ingrowth surface provided some immediate advantages for endplate osseointegration as there was no evidence of implant subluxation, despite immediate post-operative unrestricted cervical activity. Following cervical disc replacement, histological osseointegration at the implant-bone interface is possible, while preserving segmental motion.
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Cervical disc replacement-porous coated motion Prosthesis: a comparative biomechanical analysis showing the key role of the posterior longitudinal ligament.
Spine, 2003Co-Authors: Paul C Mcafee, Anton E. Dmitriev, Niabin Hu, Andy Cappuccino, L PimentaAbstract:STUDY DESIGN: Benchtop cadaveric biomechanical comparative testing and caprine animal model in vivo implantation. OBJECTIVE: To evaluate the role of the posterior longitudinal ligament in cervical arthroplasty and to understand the relative contribution of this ligament in nonfusion applications. SUMMARY OF BACKGROUND DATA: Rauschning refers to the posterior longitudinal ligament as "The Kleenex Ligament" due to its apparent anatomic insignificance. White and Panjabi found the posterior longitudinal ligament ranked only fourth in importance in tensile load-to-failure biomechanical testing. In the postoperative situation following anterior cervical diskectomy fusion, posterior longitudinal ligament integrity is overlooked by physicians because the entire disc space usually fuses into a homogeneous block of bone. PURPOSE: This biomechanical study was undertaken to determine the relative importance of the posterior longitudinal ligament following two different degrees of anterior decompression, anterior disc replacement, and anterior arthrodesis procedures. METHODS: A total of seven fresh frozen human cadaveric cervical spines (C3-C7) (mean age 68 +/- 19 years) were used for biomechanical testing. Each vertebra was equipped with three non-colinear light emitting diodes designed for detection by an optoelectronic motion measurement system (3020 Optotract System). To determine the multidirectional flexibility, six pure moments (flexion, extension, right + left lateral bending, right + left axial rotation) and axial compression were applied using a servohydraulic 858 Bionix testing device configured with a six-degree-of-freedom spine simulator. Range of motion was defined as the peak displacement from the initial neutral position to the maximum load, whereas the neutral zone represents the motion from the initial neutral position to the unloaded position at the beginning of the third cycle. Seven groups of (N = 7 each) constructs at C5-C6 were: 1) intact "native" C5-C6 level; 2) anterior diskectomy (posterior longitudinal ligament intact); 3) a Low Profile Porous Coated Motion cervical disc replacement; 4) posterior longitudinal ligament resected; 5) Porous Coated Motion cervical disc replacement fixed with anterior flanges and screws; 6) tricortical structural allograft; and 7) an anterior cervical translational plate + allograft. The caprine model was evaluated for suitability as an animal model with 12 goats undergoing C3-C4 anterior cervical Porous Coated Motion disc replacement. RESULTS: Group 2 (anterior diskectomy alone) was significantly more stable than Group 4 (anterior diskectomy + posterior longitudinal ligament resection) in flexion-extension, 18.7 +/- 4.76 degrees versus 24.8 +/- 4.42 degrees (P < 0.05) and in lateral bending, 5.9 +/- 1.79 degrees versus 10.7 +/- 2.8 degrees (P < 0.05). The comparison for the two conditions for axial rotation, 10.4 +/- 13.9 degrees versus 13.9 +/- 2.7 degrees, and axial compression, 1.19 +/-.98 degrees versus 1.52 +/- 1.14 degrees, showed the same trend. Twelve goats undergoing porous coated motion cervical disc replacement had no evidence of Prosthesis Loosening, neurologic complications, or experienced inflammatory reactions from particulate wear debris after 6 months of implantation. DISCUSSION: This study confirms the pivotal role of the posterior longitudinal ligament in postsurgical stability of the cervical spine following anterior diskectomy. This is because the lateral anulus, uncovertebral ligaments, and lateral capsular ligaments are stretched and plastically deformed in the surgical distraction process of restoring the disc space height following anterior surgical decompression. There should be a separate determination of the range of motion of cervical disc replacements depending of the integrity and the amount of the posterior longitudinal ligament that has been resected. CLINICAL RELEVANCE: There are two basic types of total knee replacements, posterior cruciate ligament-preserving and posterior cruciate ligament-sacrificing designs. In the cervical spine, an analogous situation exists biomechanically depending on whether the posterior longitudinal ligament needs to be removed in its entirety as part of the spinal cord decompression part of the procedure--it may be helpful to conceptually differentiate between posterior longitudinal ligament-preserving and posterior longitudinal ligament-sacrificing total cervical disc replacements.
Zhantao Deng - One of the best experts on this subject based on the ideXlab platform.
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stat3 il 6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle induced aseptic Prosthesis Loosening
Biomaterials Science, 2021Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Ruiying Zhang, Shuai Wang, Qiujian ZhengAbstract:Background: Aseptic Loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic Prosthesis Loosening. Methods: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. Results: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. Conclusion: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic Loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic Loosening.
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the metal nanoparticle induced inflammatory response is regulated by sirt1 through nf κb deacetylation in aseptic Loosening
International Journal of Nanomedicine, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Qian Gao, Jianning ZhaoAbstract:Aseptic Loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic Loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic Loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of Prosthesis Loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening.
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sirt1 protects osteoblasts against particle induced inflammatory responses and apoptosis in aseptic Prosthesis Loosening
Acta Biomaterialia, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Nirong Bao, Qian Gao, Jianning ZhaoAbstract:Abstract We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic Loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic Prosthesis Loosening. Statement of Significance Aseptic Loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic Loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic Loosening and further investigated the underlying mechanism of aseptic Loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.
Zhenheng Wang - One of the best experts on this subject based on the ideXlab platform.
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stat3 il 6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle induced aseptic Prosthesis Loosening
Biomaterials Science, 2021Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Ruiying Zhang, Shuai Wang, Qiujian ZhengAbstract:Background: Aseptic Loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic Prosthesis Loosening. Methods: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. Results: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. Conclusion: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic Loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic Loosening.
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the metal nanoparticle induced inflammatory response is regulated by sirt1 through nf κb deacetylation in aseptic Loosening
International Journal of Nanomedicine, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Qian Gao, Jianning ZhaoAbstract:Aseptic Loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic Loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic Loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of Prosthesis Loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening.
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sirt1 protects osteoblasts against particle induced inflammatory responses and apoptosis in aseptic Prosthesis Loosening
Acta Biomaterialia, 2017Co-Authors: Zhantao Deng, Zhenheng Wang, Jiewen Jin, Yong Wang, Nirong Bao, Qian Gao, Jianning ZhaoAbstract:Abstract We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic Loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic Prosthesis Loosening. Statement of Significance Aseptic Loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic Loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic Loosening and further investigated the underlying mechanism of aseptic Loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.
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particle induced osteolysis mediated by endoplasmic reticulum stress in Prosthesis Loosening
Biomaterials, 2013Co-Authors: Rui Wang, Zhenheng Wang, Guoyin Liu, Hao Shi, Jiangning Chen, Lei Dong, Jianning Zhao, Junfeng ZhangAbstract:We hypothesized that endoplasmic reticulum (ER) stress in macrophages induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total hip arthroplasty (THA) failure. In the present study, the expression of ER stress markers was examined by Western blot in macrophages treated with particles from materials used in prosthetics, specimens from PIO animal models and patients suffering from aseptic Loosening. To address whether ER stress triggers these inflammatory responses, the effect of an ER stress blocker on the expression of inflammatory cytokines in particle-treated macrophages and PIO animal models was tested. The results demonstrated that ER stress markers were significantly upregulated in particle-treated macrophages, periosteum tissues from PIO animal models and clinical specimens of Prosthesis Loosening. Blocking ER stress with a specific inhibitor dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and in vivo. Furthermore, in PIO animal models, this ER stress blocker dramatically suppressed the differentiation of osteoclasts and reduced the severity of osteolysis. Thus, the results of the present study suggest that ER stress plays a key role in particle-induced osteolysis and that targeting the ER stress pathway may lead to novel therapeutic approaches for the treatment of aseptic Prosthesis Loosening.
Lei Liu - One of the best experts on this subject based on the ideXlab platform.
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hydrogen sulfide protects against particle induced inflammatory response and osteolysis via sirt1 pathway in Prosthesis Loosening
The FASEB Journal, 2020Co-Authors: Lei Liu, Ming Zhou, Ruofu Zhu, Jun Zhou, Zhidong Wang, Naicheng Liu, Feng ZhuAbstract:Wear debris-induced osteolysis and ensuing aseptic Loosening is the main cause of implant failure and revision surgery. Wear debris-induced inflammatory response plays key roles in peri-implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2 S in wear debris-induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2 S on wear debris-induced pro-inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow-releasing H2 S donor GYY4137, our study demonstrated that H2 S attenuated wear debris-induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti-inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris-induced inflammation. Collectively, these results suggested that exogenous H2 S production (via H2 S donors) may represent a potential approach for the treatment of wear particle-induced osteolysis.
