Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the "prosthetic microenvironment". In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Protein-energy malnutrition and worse outcomes after major cancer surgery: A nationwide analysis.

Background: Protein-energy malnutrition (PEM) has been recognized as a poor prognostic factor in many clinical issues. However, nationwide population studies concerning the impact of PEM on outcomes after major cancer surgery (MCS) are lacking. We aimed to evaluate the postoperative outcomes associated with PEM following MCS. Methods: By using the Nationwide Inpatient Sample database, data of patients undergoing MCS including colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were analyzed retrospectively from 2009 to 2015, resulting in a weighted estimate of 1,335,681 patients. The prevalence trend of PEM, as well as mortality and major complications after MCS were calculated. Multivariable regression analysis was applied to estimate the impact of PEM on postoperative outcomes after MCS. Results: PEM showed an estimated annual percentage increase of 7.17% (95% confidence interval (CI): 4-10.44%) from 2009 to 2015, which contrasts with a 4.52% (95% CI: -6.58-2.41%) and 1.21% (95% CI: -1.85-0.56%) annual decrease in mortality and major complications in patients with PEM after MCS. PEM was associated with increased risk of mortality (odds ratio (OR)=2.26; 95% CI: 2.08-2.44; P < 0.0001), major complications (OR=2.46; 95% CI: 2.36-2.56; P < 0.0001), higher total cost ($35814 [$22292, $59579] vs. $16825 [$11393, $24164], P < 0.0001), and longer length of stay (14 [9-21] days vs. 4 [2-7] days, P < 0.0001), especially in patients underwent prostatectomy, hysterectomy and lung resection. Conclusions: PEM was associated with increased worse outcomes after major cancer surgery. Early identification and timely medical treatment of PEM for patients with cancer are crucial for improving postoperative outcomes.

Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo.

Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1-5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening.

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.

Perioperative patient-specific factors-based nomograms predict short-term periprosthetic bone loss after total hip arthroplasty.

BACKGROUND: Although medical intervention of periprosthetic bone loss in the immediate postoperative period was recommended, not all the patients experienced periprosthetic bone loss after total hip arthroplasty (THA). Prediction tools that enrolled all potential risk factors to calculate an individualized prediction of postoperative periprosthetic bone loss were strongly needed for clinical decision-making. METHODS: Data of the patients who underwent primary unilateral cementless THA between April 2015 and October 2017 in our center were retrospectively collected. Candidate variables included demographic data and bone mineral density (BMD) in spine, hip, and periprosthetic regions that measured 1 week after THA. Outcomes of interest included the risk of postoperative periprosthetic bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year. Nomograms were presented based on multiple logistic regressions via R language. One thousand Bootstraps were used for internal validation. RESULTS: Five hundred sixty-three patients met the inclusion criteria were enrolled, and the final analysis was performed in 427 patients (195 male and 232 female) after the exclusion. The mean BMD of Gruen zone 1, 7, and total were decreased by 4.1%, 6.4%, and 1.7% at the 1st year after THA, respectively. 61.1% of the patients (261/427) experienced bone loss in Gruen zone 1 at the 1st postoperative year, while there were 58.1% (248/427) in Gruen zone 7 and 63.0% (269/427) in Gruen zone total. Bias-corrected C-index for risk of postoperative bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year were 0.700, 0.785, and 0.696, respectively. The most highly influential factors for the postoperative periprosthetic bone loss were primary diagnosis and BMD in the corresponding Gruen zones at the baseline. CONCLUSIONS: To the best of our knowledge, our study represented the first time to use the nomograms in estimating the risk of postoperative periprosthetic bone loss with adequate predictive discrimination and calibration. Those predictive models would help surgeons to identify high-risk patients who may benefit from anti-bone-resorptive treatment in the early postoperative period effectively. It is also beneficial for patients, as they can choose the treatment options based on a reasonable expectation following surgery.

How to predict early clinical outcomes and evaluate the quality of primary total knee arthroplasty: a new scoring system based on lower-extremity angles of alignment.

BACKGROUND: A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient's surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. METHODS: We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. RESULTS: We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: "A" = PGGCO ≥0.8, "B" = PGGCO ≤0.6 but < 0.8, and "C" = PGGCO < 0.6. The scoring system performed well in external validation. CONCLUSIONS: This study first developed a validated, evidence-based scoring system based on lower-extremity angles of alignment to predict early clinical outcomes and to objectively evaluate the quality of TKA.

The application of thromboelastography in risk stratification for selective thromboembolism prophylaxis after total joint arthroplasty in Chinese: a randomized controlled trial.

BACKGROUND: As Asian populations, Chinese have a lower rate of high-risk gene mutations in venous thrombosis. Therefore, individual patient risk assessment, rather than a "blanket policy", is considered the best thromboembolism prophylaxis for Chinese. The purpose of this study was to evaluate the effectiveness and safety of selective thromboembolism prophylaxis compared with conventional thromboembolism prophylaxis by risk stratification with thromboelastography (TEG) after joint arthroplasty in Chinese. METHODS: Between August 2016 to August 2017, Chinese patients who underwent hip or knee arthroplasty were randomly divided into a selective anticoagulation group (SAG) and a conventional anticoagulation group (CAG). Participants and outcome assessors were blinded. In the SAG, an anticoagulant was used when TEG indicated hypercoagulability; while in the CAG, an anticoagulant was regularly used until one month after surgery. Outcome evaluation included effectiveness (defined as the incidence of VTE), and safety (defined as the incidence of bleeding events, poor wound healing, blood loss, and infection). RESULTS: A total of 197 patients (79 in the SAG and 118 in the CAG) were included in the study. There was 1 case of deep vein thrombosis (DVT) in the SAG and 2 cases of DVT in the CAG, but there was no significant difference between the two groups. Hidden blood loss in the SAG was 707.4±539.8 mL and hidden blood loss in the CAG was 617±565.0 mL, respectively (P>0.05). No significant difference was observed in perioperative blood loss between the SAG and the CAG (1,024.9±597.9 and 1,139.3±620.9 mL, respectively). Volume of blood transfusion was 92.4±270.2 mL in the SAG and 224.6±416.3 mL in the CAG, respectively, while rate of transfusion was 13.9% in the SAG and 33.9% in the CAG, respectively, which were significantly different between the two groups (P<0.05). CONCLUSIONS: In Chinese patients who underwent hip or knee arthroplasty, the efficacy of selective anticoagulation using TEG in risk stratification was comparable to that of conventional anticoagulation. Furthermore, the safety of selective anticoagulant prophylaxis was superior to that of conventional anticoagulant prophylaxis.

Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database.

BACKGROUND: Both diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM). METHODS: We used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses. RESULTS: A weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62-0.81), death (OR = 0.64, 95% CI 0.52-0.78), acute kidney injury (OR = 0.66, 95% CI 0.62-0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42-0.50). CONCLUSIONS: Prior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.

10-year follow-up results of the prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of the femoral head.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) is a severely disabling disease of the hip. Several clinical trials have shown promising outcomes on the use of mesenchymal stem cells for the treatment of ANFH, but long-term clinical assessments are lacking. Previously, we reported the 2-year follow-up results of a prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with ANFH. Here, we report the 10-year follow-up results of this study. METHODS: We recruited 43 (53 hips) patients from 2009 to 2010. The hips were randomly allocated to code decompression (CD) with or without bone marrow buffy coat (BBC) grafting. Participants underwent follow-up at 24, 60, and 120 months postoperatively. The visual analogue scale (VAS), Lequesne algofunctional index, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scores were recorded. Survival rate analysis and prognostic factor analysis were performed. The endpoint was defined as progression to Ficat stage IV or conversion to hip arthroplasty. RESULTS: A total of 31 patients (41 hips) were included in the final analysis. The CD + BBC group had better subjective assessment scores than the CD group. The average survival times were 102.3 months and 78.1 months in the CD + BBC group and CD group, respectively (log-rank test, P = 0.029). In the univariate Cox proportional hazards regression model, age [hazard ratio (HR) = 1.079, P = 0.047] and preoperative Ficat stage (HR = 3.283, P = 0.028) indicated a high risk for progression, while the use of BBC (HR = 0.332, P = 0.042) indicated a low risk. Preoperative Ficat stage III was isolated as an independent risk factor for clinical failure in the multivariate model (HR = 3.743, P = 0.018). CONCLUSION: The 10-year follow-up results of this prospective, double-blinded, randomized, controlled study showed that the use of autologous BBC in combination with core decompression was more effective than the use of core decompression alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01613612 . Registered on 13 December 2011-retrospectively registered.

Prediction of Early Postoperative Major Cardiac Events and In-Hospital Mortality in Elderly Hip Fracture Patients: The Role of Different Types of Preoperative Cardiac Abnormalities on Echocardiography Report.

INTRODUCTION: Transthoracic echocardiography (TTE) is a common cardiac screening test before hip fracture surgery. However, the general TTE test delays surgery, so it would be meaningful if we could simplify the TTE by only assessing cardiac abnormality specifically. Therefore, we aimed to establish the most clinically relevant abnormality by comparing the predictive value of each major cardiac abnormality in postoperative cardiac complications and mortality in elderly hip fracture patients. PATIENTS AND METHODS: From January 2014 to January 2019, the medical records of all surgically treated elderly patients (>65 years) with hip fracture were analyzed. The major TTE abnormalities were defined as left ventricular hypertrophy, systolic pulmonary arterial pressure >25 mm Hg, moderate-severe valve abnormality, left ventricular ejection fraction (LVEF) <50%, and pericardial effusion. The outcomes were postoperative cardiac complications and in-hospital mortality. RESULTS: There were 354 patients involved finally. Postoperative cardiac complications were encountered in 7.6% (n=27) of patients. The mortality rate was 2.8% (n=10). History of coronary artery disease (CAD) (OR: 3.281, 95% CI: 1.332-8.079, p=0.010) and presence of aortic stenosis (AS) (OR:5.656, 95% CI: 1.869-17.117, p=0.002) were independent predictors of postoperative cardiac complications. In addition, age (OR: 1.264, 95% CI: 1.047-1.527, p=0.015), history of CAD (OR: 19.290, 95% CI: 2.002-185.885, p=0.010), presence of AS (OR:7.164, 95% CI: 1.988-51.413, p=0.040) and LVEF <50% (OR:8.803, 95% CI: 1.115-69.472, p=0.039) were independent predictors of mortality. However, the rest of preoperative TTE abnormalities were not associated with postoperative cardiac complications or mortality. CONCLUSION: Among the TTE abnormalities presented by elderly patients with hip fracture, moderate-severe AS was the predictor of postoperative cardiac complications. Moreover, moderate-severe AS and LVEF <50% were the predictors of in-hospital mortality. Therefore, we could simplify the TTE process by assessing aortic valve and LVEF specifically on focused echocardiography, which could avoid surgery delay.

The Immune Cell Landscape in Different Anatomical Structures of Knee in Osteoarthritis: A Gene Expression-Based Study.

BACKGROUND: Immunological mechanisms play a vital role in the pathogenesis of knee osteoarthritis (KOA). Moreover, the immune phenotype is a relevant prognostic factor in various immune-related diseases. In this study, we used CIBERSORT for deconvolution of global gene expression data to define the immune cell landscape of different structures of knee in osteoarthritis. Methods and Findings. By applying CIBERSORT, we assessed the relative proportions of immune cells in 76 samples of knee cartilage, 146 samples of knee synovial tissue, 40 samples of meniscus, and 50 samples of knee subchondral bone. Enumeration and activation status of 22 immune cell subtypes were provided by the obtained immune cell profiles. In synovial tissues, the differences in proportions of plasma cells, M1 macrophages, M2 macrophages, activated dendritic cells, resting mast cells, and eosinophils between normal tissues and osteoarthritic tissues were statistically significant (P < 0.05). The area under the curve was relatively large in resting mast cells, dendritic cells, and M2 macrophages in receiver operating characteristic analyses. In subchondral bones, the differences in proportions of resting master cells and neutrophils between normal tissues and osteoarthritic tissues were statistically significant (P < 0.05). In subchondral bones, the proportions of immune cells, from the principle component analyses, displayed distinct group-bias clustering. Resting mast cells and T cell CD8 were the major component of first component. Moreover, we revealed the potential interaction between immune cells. There was almost no infiltration of immune cells in the meniscus and cartilage of the knee joint. CONCLUSIONS: The immune cell composition in KOA differed substantially from that of healthy joint tissue, while it also differed in different anatomical structures of the knee. Meanwhile, activated mast cells were mainly associated with high immune cell infiltration in OA. Furthermore, we speculate M2 macrophages in synovium and mast cells in subchondral bone may play an important role in the pathogenesis of OA.

Hydrogen sulfide protects against particle-induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening.

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-1ß (IL-1ß), 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.

High periprosthetic bone mineral density measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless total hip arthroplasty - A retrospective study.

BACKGROUND: Total hip arthroplasty is the most common orthopaedic procedure for the end-stage hip diseases. Periprosthetic bone loss is closely related to the increased risk of implant loosening and periprosthetic fractures, but the predictive value of periprosthetic bone mineral density (BMD) measured immediately after surgery has not yet been investigated. METHODS: From April 2015 to October 2017, 64 patients with femoral neck fracture, hip osteoarthritis, femoral head necrosis, or developmental dysplasia of the hip underwent unilateral total hip arthroplasty. Demographic data, bone mineral density of the hip and spine, periprosthetic BMD of 7 Gruen zones, and radiographic parameters measured preoperatively, 1 week, 3 months, and 12 months after surgery were collected. A p value < 0.05 was considered to be statistically significant. RESULTS: Significant decreases of the periprosthetic BMD were found in Gruen zone 1 (- 8.0%; p < 0.05), Gruen zone 2 (- 6.3%; p < 0.05), Gruen zone 7 (- 8.6%; p < 0.05), and total Gruen zone (- 4.7%; p < 0.05) in the first postoperative year, compared with the values measured 1 week after surgery. The relationship between the preoperative BMD of the hip/spine and the BMD of Gruen zone 1 and Gruen zone 7 measured 1 week after surgery did not reach statistical significance. The multiple linear regression analysis illustrated that the bone loss in Gruen zone 7 at the end of the follow-up period was negatively affected (ß = - 0.703) by the BMD of Gruen zone 7 measured 1 week after surgery, with a R2 of 0.486 (p < 0.05). Similar results were also found in Gruen zone 1 (ß = - 0.448, R2 = 0.186; p < 0.05). CONCLUSION: There were marked decreases in periprosthetic BMD of the proximal femur in the first postoperative year. The predictive values of preoperative BMD of hip and spine on periprosthetic bone loss after THA were limited. Higher periprosthetic BMD measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless THA.

Impact of Bariatric Surgery on Inpatient Complication, Cost, and Length of Stay Following Total Hip or Knee Arthroplasty.

BACKGROUND: Morbid obesity is an important risk factor for arthroplasty and also closely associated with worse postoperative outcomes. Bariatric surgery is effective in losing weight and decreasing comorbidities associated with obesity. However, no study had demonstrated the influence of bariatric surgery on the outcome of arthroplasty in a large population. METHODS: We used 2006-2014 discharge records from the Nationwide Inpatient Sample, and identified study population and inpatient complications by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis/procedure codes. Propensity score analysis was used to match total hip arthroplasty (THA) or total knee arthroplasty (TKA) patients with morbid obesity and THA or TKA patients with bariatric surgery. RESULTS: Proportion of morbid obesity in both TKA and THA patients demonstrated a rising trend, while proportion of bariatric surgery in morbidly obese TKA and THA patients remains steady after 2007. For THA patients, there was fewer pulmonary embolism, more blood transfusion and anemia, and shorter length of stay in bariatric surgery group. For TKA patients, bariatric surgery group had a lower risk of pulmonary embolism, respiratory complications, death, and shorter length of stay, but bariatric surgery group had a higher risk of blood transfusion and anemia. CONCLUSION: There is evidence that bariatric surgery prior to arthroplasty, especially THA, appears to reduce rates of pulmonary complications and length of stay. But anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

Construction and Evaluation of a Murine Calvarial Osteolysis Model by Exposure to CoCrMo Particles in Aseptic Loosening.

Wear particle-induced osteolysis is a major cause of aseptic loosening in arthroplasty failure, but the underlying mechanism remains unclear. Due to long follow-ups necessary for detection and sporadic occurrence, it is challenging to assess the pathogenesis ofparticle-induced osteolysis in clinical cases. Hence, optimal animal models are required for further studies. The murine model of calvarial osteolysis established by exposure to CoCrMo particles is an effective and valid tool for assessing the interactions between particles and various cells in aseptic loosening. In this model, CoCrMo particles were first obtained by high-vacuum three-electrode direct current and resuspended in phosphate-buffered saline at a concentration of 50 mg/mL. Then, 50 µL of the resulting suspension was applied to the middle of the murine calvaria after separation of the cranial periosteum by sharp dissection. After two weeks, the mice were sacrificed, and calvaria specimens were harvested; qualitative and quantitative evaluations were performed by hematoxylin and eosin staining and micro computed tomography. The strengths of this model include procedure simplicity, quantitative evaluation of bone loss, rapidity of osteolysis development, potential use transgenic or knockout models, and a relatively low cost. However, this model cannot to be used to assess the mechanical force and chronic effects of particles in aseptic loosening. Murine calvarial osteolysis model generated by exposure to CoCrMo particles is an ideal tool for assessing the interactions between wear particles and various cells, e.g., macrophages, fibroblasts, osteoblasts and osteoclasts, in aseptic loosening.

Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice.

Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specialist visits were collected. A mouse model of osteomyelitis was used to verify the presence of impaired glucose metabolism and depression. All data were processed by SPSS. Results: The incidence of T2DM was 2.37-fold higher in patients with COM than in those without. In COM patients, subjects with T2DM (DDM) had higher BMI, less exercise and more frequent visits to specialists than those without (Con). Glucose and lipid metabolism were worse in patients with DDM. Patients with DDM had higher levels of white blood cells (12.9±2.1×109/L vs. 11.7±2.2×109/L, p=0.027), CRP (28.4±4.5 mg/L vs. 22.0±4.8 mg/L, p<0.001), TNF-α (13.5±5.0 pg/mL vs. 9.4±2.6 pg/mL, p= 0.003) and IL-6 (12.9±3.2 pg/mL vs. 9.2±2.7 pg/mL, p<0.001). Significantly increased fasting blood glucose concentrations and impairment of oral glucose tolerance tests were also observed in mice modelling osteomyelitis, which were accompanied by elevated TNF-α and IL-6 levels. Furthermore, the proportion of depression (63.2% vs. 35.2%, p=0.003) and severe anxiety (31.6% vs. 9.1%, p=0.002) were significantly higher in the DDM group. Osteomyelitis mice showed obvious depressive-like behaviours. The levels of TNF-α, IL-6, CRP, BMI, and LDL; lack of exercise; SAS; HAQ; and SF36 assessment were risk factors for the development of T2DM in COM patients. Conclusions: Chronic osteomyelitis increased the incidence of T2DM in both humans and mice. Inflammation, mental illness and lack of exercise were risk factors for the occurrence of T2DM in osteomyelitis. Comprehensive consideration of patient history, including metabolism and mental health, is needed in planning future treatment.

Probiotics protect mice from CoCrMo particles-induced osteolysis.

Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs)-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis.