The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces.

With the continuous innovation and breakthrough of nanomedical technology, stimuli-responsive nanotechnology has been gradually applied to the surface modification of titanium implants to achieve brilliant antibacterial activity and promoted osteogenesis. Regarding to the different physiological and pathological microenvironment around implants before and after surgery, these surface nanomodifications are designed to respond to different stimuli and environmental changes in a timely, efficient, and specific way/manner. Here, we focus on the materials related to stimuli-responsive nanotechnology on titanium implant surface modification, including metals and their compounds, polymer materials and other materials. In addition, the mechanism of different response types is introduced according to different activation stimuli, including magnetic, electrical, photic, radio frequency and ultrasonic stimuli, pH and enzymatic stimuli (the internal stimuli). Meanwhile, the associated functions, potential applications and developing prospect were discussion.

Surface sulfonation and nitrification enhance the biological activity and osteogenesis of polyetheretherketone by forming an irregular nano-porous monolayer.

Polyether-ether-ketone (PEEK) is becoming a popular component of clinical spinal and orthopedic applications, but its practical use suffers from several limitations. In this study, irregular nano-porous monolayer with differently functional groups was formed on the surface of PEEK through sulfonation and nitrification. The surface characteristics were detected by field-emission scanning electron microscopy, atomic force microscopy, energy-dispersive X-ray spectrometry, water contact angle measurements and Fourier transform infrared spectroscopy. In vitro cellular behaviors were evaluated by cell adhesion, morphological changes, proliferation, alkalinity, phosphatase activity, real-time RT-PCR and western blot analyses. In vivo osseointegration was examined through micro-CT and histological assessments. Our results reveal that the irregular nano-porous of PEEK affect the biological properties. High-temperature hydrothermal NP treatment induced early osteogenic differentiation and early osteogenesis. Modification by sulfonation and nitrification can broaden the use of PEEK in orthopedic and dental applications. This study provides a theoretical basis for the wider clinical application of PEEK. a To obtain a uniform porous structure, PEEK samples were treated by concentrated sulfuric acid and fuming nitric acid (82-80%) with magnetic stirring sequentially. b Effects of nanopores on biological behavior of bMSCS.

Effects of sleep deprivation on pain-related factors in the temporomandibular joint.

BACKGROUND: The objective of this study was to investigate the effects of experimental sleep deprivation (SD) on the temporomandibular joint (TMJ) in rats by examining pain-related factors and to determine the possible involvement of estrogen and NF (nuclear factor) κB signaling in the TMJ synovial membrane. METHODS: The influence of SD, conducted in rats using the modified multiple platform method, was estimated by observing behavioral manifestations and examining changes in serum hormone levels. The morphologic changes of synovial tissue were observed with light microscopy and the serum levels of estrogen were measured by radioimmunoassay. Activation of NF-κB in the synovial membrane was examined using an immunofluorescence technique, and the expression levels of interleukin (IL) 1ß, IL-6, tumor necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase were measured with real-time polymerase chain reaction. RESULTS: The SD group showed evidence of elevated anxiety and stress, and increased plasma levels of estradiol compared with the control group. The activity of NF-κB was significantly enhanced and translocation of NF-κB p65 was evident in the synovial membrane after SD. The expression of pain-related factors IL-1ß, IL-6, cyclooxygenase-2, tumor necrosis factor α, and inducible nitric oxide synthase in the synovial membrane significantly increased after SD. CONCLUSIONS: These results indicate that SD increases serum levels of estrogen and induces alterations in pain-related factors in the TMJ. The NF-κB pathway has been associated with the regulation of these inflammatory cytokines and plays an important role in temporomandibular disorders.

Effects of endoplasmic reticulum stress on chondrocyte apoptosis via the PI3K/AKT signaling pathway.

Chondrocytes undergo endoplasmic reticulum stress (ERS)-induced apoptosis under abnormal stimulation. However, the underlying molecular mechanism remains unclear. We investigated the regulatory effect of the PI3K/AKT signaling pathway on ERS and its effect on chondrocyte apoptosis. In addition, we established a unilateral anterior crossbite (UAC) model in rats to induce temporomandibular joint osteoarthritis (TMJOA). Chondrocytes were isolated from the temporomandibular joints and treated with lipopolysaccharide (LPS) in vitro. Protein expression of ERS and apoptosis markers (GRP78 and CASP12) was analyzed by immunohistochemistry and western blotting. The expression of GRP78, CASP12, p-PI3K, and p-AKT significantly increased in the UAC group. LY294002, a PI3K/AKT signaling pathway inhibitor, reduced the protein expression of GRP78, ATF4, CHOP, and CASP12, whereas 740 Y-P, an activation agent, elevated the expression of proteins GRP78, ATF4, CHOP, and CASP12. In the present study, UAC and LPS stimulation induced apoptosis of chondrocytes in the ERS pathway. Inhibition of the PI3K/AKT signaling pathway reduced ERS-induced chondrocyte apoptosis.

Low-intensity ultrasound accelerates mandibular implant bone integration in dogs with mandibular osteoradionecrosis.

BACKGROUND: To investigate whether low-intensity ultrasound accelerates healing in bone tissues close to dental implants with osteoradionecrosis (ORN) of the mandible and is suitable for development as a therapy in patients with dental implants receiving radiotherapy. MATERIALS AND METHODS: Dog models of radiative bone injury surrounding dental implants in both sides of mandible were established by four treatment methods of radiotherapy, each 15Gy. After radiative treatment, antibiotics were administered and the left injury was treated with ultrasound and the right with debridement. Measures for evaluation included spiral computed tomography (SCT), Micro-CT, microvessel density, and pull-out experiment, and data were collected and analyzed. RESULTS: After 4months of radiotherapy, both sides of mandible displayed preclinic symptom of radiative osteonecrosis. Microvessel density of the side treated by ultrasound was 6.2152±0.6508 and that of the debridement side was 3.8490±0.8954 (P<0.05). Micro-CT results showed that bone volume fraction of trabecula, thickness of trabecula, trabecula spacing, ratio of bone surface area to bone volume, and trabecula number of the ultrasound-treated mandible were 0.3605±0.0337, 0.0287±0.0045, 0.0369±0.0073, 71.6124±14.1649, and 7.2915±1.4937, whereas those of the debridement side were 0.1779±0.0178, 0.0151±0.0021, 0.6623±0.1125, 33.2686±5.949, and 5.0689±0.5028, respectively; statistical significance was observed (P<0.05). Pull-out experiment suggested that pull-out strength of the ultrasound-treated side was 0.5793±0.1066 whereas that of the debridement side was 0.2980±0.0243, representing a statistical significance (P<0.05). CONCLUSIONS: Low-intensity ultrasound can accelerate the healing of bone tissues surrounding dental implants in osteoradionecrosis of the mandible animals.

Psychological stress may contribute to temporomandibular joint disorder in rats.

BACKGROUND: Psychological stress is considered a possible pathogenic factor for temporomandibular joint disorders (TMJD), but few reports have supplied direct evidence. This study was designed to observe the effects of psychological stress on the masticatory muscles and condylar processes in rats to directly investigate the role of psychological stress in TMJD morbidity. MATERIALS AND METHODS: A well-established rat communication box model was used to compare the myoelectric profiles of temporal and masseter muscles and condylar microstructure among rats in a control group, a psychological stress group (PS group), and a diazepam (anxiolytic agent) injection group (PS + DI group). Reverse-transcription polymerase chain reaction was also used to analyze the substance P mRNA and calcitonin gene-related peptide mRNA levels expressed in condylar cartilages during different phases of psychological stress. RESULTS: At 1, 3, and 5 wk, both temporal and masseter muscles in the PS group exhibited a significantly higher electrical potential in relaxation than those in the control group (P < 0.01). The electrical potential during contraction of the temporal and masseter muscles was higher than in the relaxation or control group at 1, 3, and 5 wk (P < 0.01). Scanning electron microscopy demonstrated pathologic changes in condylar processes in the PS group that were not observed in the PS + DI group. Reverse-transcription polymerase chain reaction also showed that the expression of substance P and calcitonin gene-related peptide in rat temporomandibular joint was upregulated during each phase of the psychological stress (P < 0.05). CONCLUSIONS: Psychological stress may play an important role in the formation of TMJD.

Ultrasonic treatment of canine ORNM.

PURPOSE: To investigate the effect of low-intensity ultrasound on mandibular osteoradionecrosis. MATERIALS AND METHODS: Using a canine model, radiotherapy was delivered to the mandible at doses of 25 and 28 Gy. The microstructure of the mandible and changes in microvascular density in the low-intensity ultrasound treatment (group A) and nontreatment (group B) groups were determined and compared with those of the control group. RESULTS: At a single dose of 28 Gy, the canines developed epilation of the mandibular skin, ulcers, and small pieces of oral sequestered material. The microvascular density in group A was significantly greater than that in group B (P<.05). Most osteocytes in group B had disappeared, with atrophy of the cancellous bone trabeculae. In contrast, in group A, a substantial amount of bone had been formed, with increasing amounts of bone trabeculae and a large number of osteoblasts. CONCLUSIONS: Low-intensity ultrasound effectively improves the healing of irradiated bone.

Influence of different education approaches on the implantation performance of dental practitioners in aesthetic zone.

PURPOSE: To investigate the influence of different education approaches on the implantation performance (operation time, three-dimensional deviation) of inexperienced operators. METHODS: Eighteen students who met the inclusion criteria were randomly assigned to traditional training group or digital training group. After training, the average operation time and implant deviation (platform deviation, apex deviation, and angle deviation) of the two groups were calculated by Student's t-test. A self-developed questionnaire was used to evaluate the students' grasp of clinical knowledge and skill. RESULT: Compared with the traditional training group, the duration of implant installation and temporary prosthesis placement of the digital training group decreased significantly (p < 0.05). The implant deviation of the digital training group was lower than that of the traditional training group. The apex deviation (p = 0.015) and angle deviation (p = 0.015) significantly improved with digital training, but differences in platform deviation (p = 0.065) were not statistically significant. The questionnaire survey showed that the overall perception of the inexperienced operators in the digital training group was better than that in the traditional training group. CONCLUSION: In the hands of inexperienced operators, digital training reduced the operation time and improved the implant accuracy in comparison with traditional training.

Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-ß-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.

A comparison of the burden of knee osteoarthritis attributable to high body mass index in China and globally from 1990 to 2019.

Background: Excess body mass index (BMI) plays a key role in the onset and progression of knee osteoarthritis (knee OA). However, the burden of knee OA attributable to high BMI at the global, Chinese, and regional levels have received far too little attention. The aim of this study is to provide evidence to support the design of policy by investigating long-term trends of years lived with disability (YLDs) for knee OA. Methods: To illustrate the trends of YLDs for knee OA attributable to high BMI and the temporal trends of the YLDs rate by age, period, and cohort, Joinpoint regression software and age-period-cohort (APC) were used to analyze the YLDs data of knee OA from the Global Burden of Disease (GBD) 2019. Results: In China, there were 549,963.5 YLDs for knee OA attributable to high BMI in 2019, which had increased by 460.7% since 1990. From 1990 to 2019, age-standardized disability-adjusted life year rate (ASDR) of knee OA attributable to high BMI trended upwards. The average annual percent change (AAPC) of knee OA attributable to high BMI in China and globe were 3.019, 1.419%, respectively. The longitudinal age curve of the APC model showed that the YLDs rates of knee OA due to high BMI increased with age, and YLDs rates were higher among females than males. The period rate ratios (RRs) of knee OA due to high BMI increased significantly. The cohort RRs of knee OA due to high BMI increased among those born between 1900 and 1970. The net drifts of knee OA attributable to high BMI in China and globe were above 1. Compared with global condition, the net drift values of knee OA attributable to high BMI in China was higher. Compared with females, males had higher net drift value. Countries with high socio-demographic index (SDI) have a much higher burden of knee OA caused by high BMI than countries with low SDI. Conclusion: In China, high BMI is a substantial cause of knee OA, the incidence of which has been increasing since 1990. In addition, women and the elderly are more vulnerable to knee OA caused by high BMI. The Chinese government must take the long-term impact of high BMI on knee OA into account and implement effective public health policies and resort to interventions to reduce the burden as soon as possible.

The influence of psychological stress on the rat temporomandibular joint with the application of countermeasures.

OBJECTIVE: This study aimed to provide an experimental theoretical basis for the treatment of temporomandibular disorders by observing the effects of psychological stress and countermeasures on the rat temporomandibular joint (TMJ). METHODS: Rats were exposed to psychological stress via a communication box and the lateral pterygoid muscle and TMJ were observed with transmission electron microscopy and scanning electron microscopy. Furthermore, the expression of interleukin-1 and tumor necrosis factor-α was assessed in control animals and psychological stress (PS) and stress with diazepam (PS+DI) groups. RESULTS: Transmission electron microscopy of the lateral pterygoid muscle fibers in the PS showed vacuolar changes in the mitochondria, loss of cristae, and reduced matrix density to variable degrees after 1, 3, and 5 wk of stress. After 5 wk stress+recovery, the cristae and matrix were normal in the PS and PS+DI groups. Scanning electron microscopy of PS rats showed some synovial membranes were detached from the surface of the articular disc after 1 wk. After 3 wk, collagen fibers appeared to have wider waves and worn strips changing in size on the articular disc; after 5 wk, the distribution of collagen fibers was distorted. In PS+recovery and PS+DI rats, no obvious changes were observed on the surface of the articular disc after 1 to 5 wk stress. In PS rats, interleukin-1 and tumor necrosis factor-α expression increased significantly but was at control levels in the PS+DI and PS+recovery groups. CONCLUSION: Counteracting psychological stress can antagonize its effects on the TMJ and provide a reference for the treatment of stress-related temporomandibular disorders.

Animal Models of Temporomandibular Joint Osteoarthritis: Classification and Selection.

Temporomandibular joint osteoarthritis (TMJOA) is a common degenerative joint disease that can cause severe pain and dysfunction. It has a serious impact on the quality of lives of patients. Since mechanism underlying the pathogenesis of TMJOA is not fully understood, the development of effective tools for early diagnosis and disease-modifying therapies has been hindered. Animal models play a key role in understanding the pathological process of diseases and evaluating new therapeutic interventions. Although some similarities in disease processes between animals and humans are known, no one animal model is sufficient for studying all characteristics of TMJOA, as each model has different translatability to human clinical conditions. For the past 4 decades, TMJOA animal models have been studied by numerous researchers and can be broadly divided into induced, naturally occurring, and genetically modified models. The induced models can be divided into invasive models (intra-articular injection and surgical induction) or non-invasive models (mechanical loading, high-fat diet, and sleep deprivation). Different types of animal models simulate different pathological expressions of TMJOA and have their unique characteristics. Currently, mice, rats, and rabbits are commonly used in the study of TMJOA. This review sought to provide a general description of current experimental models of TMJOA and assist researchers in selecting the most appropriate models for different kinds of research.

Whole-transcriptome sequencing and ceRNA interaction network of temporomandibular joint osteoarthritis.

Purpose: The aim of this study was to conduct a comprehensive transcriptomic analysis to explore the potential biological functions of noncoding RNA (ncRNAs) in temporomandibular joint osteoarthritis (TMJOA). Methods: Whole transcriptome sequencing was performed to identify differentially expressed genes (DEGs) profiles between the TMJOA and normal groups. The functions and pathways of the DEGs were analyzed using Metascape, and a competitive endogenous RNA (ceRNA) network was constructed using Cytoscape software. Results: A total of 137 DEmRNAs, 65 DEmiRNAs, 132 DElncRNAs, and 29 DEcircRNAs were identified between the TMJOA and normal groups. Functional annotation of the DEmRNAs revealed that immune response and apoptosis are closely related to TMJOA and also suggested key signaling pathways related to TMJOA, including chronic depression and PPAR signaling pathways. We identified vital mRNAs, including Klrk1, Adipoq, Cryab, and Hspa1b. Notably, Adipoq expression in cartilage was significantly upregulated in TMJOA compared with normal groups (10-fold, p < 0.001). According to the functional analysis of DEmRNAs regulated by the ceRNA network, we found that ncRNAs are involved in the regulation of autophagy and apoptosis. In addition, significantly DEncRNAs (lncRNA-COX7A1, lncRNA-CHTOP, lncRNA-UFM1, ciRNA166 and circRNA1531) were verified, and among these, circRNA1531 (14.5-fold, p < 0.001) and lncRNA-CHTOP (14.8-fold, p < 0.001) were the most significantly downregulated ncRNAs. Conclusion: This study showed the potential of lncRNAs, circRNAs, miRNAs, and mRNAs may as clinical biomarkers and provides transcriptomic insights into their functional roles in TMJOA. This study identified the transcriptomic signatures of mRNAs associated with immunity and apoptosis and the signatures of ncRNAs associated with autophagy and apoptosis and provides insight into ncRNAs in TMJOA.

Corrigendum: Circadian rhythm protein Bmal1 modulates cartilage gene expression in temporomandibular joint osteoarthritis via the MAPK/ERK pathway.

[This corrects the article DOI: 10.3389/fphar.2020.527744.].

Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes.

Temporomandibular joint osteoarthritis (TMJ-OA) is one of the most common joint diseases. It causes severe pain and poor quality of life. One key feature of TMJ-OA is degeneration of the chondrocyte extracellular matrix (ECM). Low-intensity pulsed ultrasound (LIPUS) can promote the synthesis of ECM in cartilage. However, the exact mechanism is still unclear. We aimed to explore the mechanism by which LIPUS promotes the expression of aggrecan in chondrocytes. In vivo, TMJ-OA rats established by unilateral occlusal trauma were treated with LIPUS. In our RNA sequencing data, we found that ADAMTS-8 was downregulated by LIPUS. In vitro, chondrocytes were treated with IL-1ß and LIPUS. Among Zn2+ exporters, ZNT-9 was specifically upregulated by LIPUS. Activation of ZNT-9 by LIPUS downregulated ECM-degrading enzymes (MMP-3, ADAMTS-5 and ADAMTS-8) and metal regulatory transcription factor-1 (MTF-1) and upregulated aggrecan in chondrocytes. Furthermore, ZNT-9 knockdown caused upregulation of MMP-3, ADAMTS-5, ADAMTS-8 and MTF-1, with concomitant downregulation of aggrecan. The opposite results were obtained after ZNT-9 overexpression. Our experiments demonstrate that LIPUS protects chondrocytes by increasing the expression of aggrecan through ZNT-9.

The Optimal Regimen for the Treatment of Temporomandibular Joint Injury Using Low-Intensity Pulsed Ultrasound in Rats with Chronic Sleep Deprivation.

Low-intensity pulsed ultrasound (LIPUS) is an emerging physical therapy for the treatment of early temporomandibular joint injury and has a good effect on promoting cartilage and subchondral bone tissue repair. However, the best LIPUS intensity and treatment duration remain unclear. This study is aimed at observing the preventive and therapeutic effects of different modes of LIPUS and at identifying the optimal LIPUS treatment regimen for temporomandibular joint injury. In the present study, rat models of temporomandibular joint injury were established using a chronic sleep deprivation (CSD) method, and the effect of LIPUS as intensities of 30, 45, and 60 mW/cm2 was observed at 7, 14, and 21 days. After CSD, the condylar cartilage of the rats demonstrated variable degrees of surface roughening, collagen fiber disarrangement or even partial exfoliation, decreased proteoglycan synthesis and cartilage thickness, decreased chondrocyte proliferation, decreased type 2 collagen (COL-2) expression, and increased matrix metalloproteinase- (MMP-) 3 expression at all three time points. When the rats with CSD received different intensities of LIPUS treatment, the pathological changes were alleviated to various extents. The groups receiving 45 mW/cm2 LIPUS showed the most significant relief of cartilage damage, and this significant effect was observed on days 14 and 21. These results demonstrated that LIPUS can effectively inhibit CSD-induced condylar cartilage damage in rats, and LIPUS treatment at an intensity of 45 mW/cm2 for at least 2 weeks is the optimal regimen for temporomandibular joint injury.

Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation.

Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis.

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway.

The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, p-ERK, and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the p-ERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.

Does tourniquet use affect the periprosthetic bone cement penetration in total knee arthroplasty? A meta-analysis.

BACKGROUND: A tourniquet is a device commonly used to control massive hemorrhage during knee replacement surgery. However, the question remains whether the use of tourniquets affects the permeability of the bone cement around the knee prosthesis. Moreover, the long-term effects and stability of the knee prosthesis are still debatable. The aim of this study was to examine whether the use of a tourniquet increases the thickness of the cement mantle and affects the postoperative blood loss and pain during primary total knee arthroplasty (TKA) using meta-analysis. METHODS: We searched the Cochrane Central Library, MEDLINE, Embase, PubMed, CNKI, and Wang Fang databases for randomized controlled trials (RCTs) on primary TKA, from inception to November 2019. All RCTs in primary TKA with and without a tourniquet were included. The meta-analysis was conducted using RevMan 5.2 software. RESULTS: A total of eight RCTs (677 knees) were analyzed. We found no significant difference in the age and sex of the patients. The results showed that the application of tourniquet affects the thickness of the bone cement around the tibial prosthesis (WMD = 0.16, 95%CI = 0.11 to 0.21, p < 0.00001). However, in our study, there was no significant difference in postoperative blood loss between the two groups was observed (WMD = 12.07, 95%CI = - 78.63 to 102.77, p = 0.79). The use of an intraoperative tourniquet can increase the intensity of postoperative pain (WMD = 1.34, 95%, CI = 0.32 to 2.36, p = 0.01). CONCLUSIONS: Tourniquet application increases the thickness of the bone cement around the prosthesis and may thus increase the stability and durability of the prosthesis after TKA. The application of an intraoperative tourniquet can increase the intensity of postoperative pain.