The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration.
Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin–mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.
ObjectiveChronic low-grade inflammation has long been recognized as the central link between obesity and type 2 diabetes (T2D). The novel subset of T helper (Th) cells, Th22, plays an emerging role in chronic inflammation. We investigated the potential association between Th22 and the pathogenesis of obesity and T2D.MethodsNinety T2D inpatients (T2D group), 30 healthy participants with BMI ranged from 19 to 23.9 kg/m2 (CTL group) and 30 metabolically healthy obese controls with BMI ≥ 30 kg/m2 (MHO group) were employed in our study. Peripheral frequencies of Th22 and Th1 and Th17 cells were determined by flow cytometry based on their specific cytokine patterns. Cytokine levels in fresh plasma were quantified by ELISA.ResultsCompared to that in CTL group (1.18±0.06%, n = 28), peripheral frequency of Th22 cells was significantly increased in MHO group (1.88±0.10%, n = 30) and in T2D group (2.247±0.10%, n = 89). There was a consistent notable increase in plasma interleukin (IL)-22 of T2D patients [47.56 (30.55–76.89) pg/mL] as compared with that of MHO group [36.65 (29.52–55.70) pg/ml; *P<0.0001] and CTLs [36.33 (31.93–40.62) pg/mL; *P<0.0001]. Furthermore, other than Th1/Th17, previously frequently described participants in obesity and T2D, there was a strong correlation between Th22 frequency and the homeostasis model of assessment for insulin resistance index (r = 0.6771, *P<0.0001) and HOMA for β-cell function (r = −0.7264, *P<0.0001).ConclusionsThere were increased Th22 frequencies and IL-22 levels in obesity and T2D. Elevated Th22 and IL-22 also aided in the differentiation of MHO from T2D patients. The notable correlation implied that Th22 might play a more determinant role in both insulin resistance and β-cell impairment.
PurposeThe purpose of this hospital-based case–control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.MethodFrom January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs).ResultsDemographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77–16.97; p = 0.003), age (65–75 vs. 45–65 years) (OR = 3.36, 95% CI: 1.30–8.69; p = 0.013), BMI (≥28 vs. 18.5–28 kg/m2) (OR = 2.77, 95% CI: 1.20–6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13–6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06–8.23; p = 0.039).ConclusionPatients with diabetes, older age, BMI of ≥28 kg/m2 and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.
Osteoarthritis (OA) is one of the most widespread degenerative joint diseases affecting the elderly. Research into the regulatory mechanisms underlying the pathogenesis of OA is therefore warranted, and over the past decade, there has been an increased focus on the functional role of microRNAs (miRNAs or miRs). In this systematic review, we aimed to review the evidence implicating miRNAs in the pathogenesis of chondrogenesis and OA. Systematic reviews of PubMed and Embase were performed to search for studies using strings of miRNAs, non-coding RNAs, cartilage, chondrocytes, chondrogenesis, chondrocytogenesis and OA. The identified studies were retrieved, and the references provided were searched. The selected studies were required to focus on the role of miRNAs in chondrogenesis and OA. The results of this review indicated that more than 25 miRNAs have been implicated in chondrogenesis and OA. In particular, chondrocytogenesis, chondrogenic differentiation, chondrocyte proliferation, chondrocyte hypertrophy, endochondral ossification, and proteolytic enzyme regulation are targeted or facilitated by more than 1 miRNA. To date, limited efforts have been performed to evaluate translational applications for this knowledge. Novel therapeutic strategies have been developed and are under investigation to selectively modulate miRNAs, which could potentially enable personalized OA therapy. miRNAs appear to be important modulators of chondrogenesis and OA. Their expression is frequently altered in OA, and many are functionally implicated in the pathogenesis of the disease. The translational roles and therapeutic potential of miRNAs remains to be evaluated.
bThis meta-analysis included 12 studies that evaluated sonication fluid cultures (SFC) for the diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.74 to 0.84) and 0.95 (CI, 0.90 to 0.98), respectively. Subgroup analyses showed that a 14-day anaerobic culture may improve sensitivity, the use of centrifugation or vortexing may improve specificity, and the use of 400 to 500 ml of Ringer's solution for containers may improve sensitivity and specificity. The best SFC cutoff was >5 CFU. In conclusion, SFC has high sensitivity and very high specificity for diagnosing PJI. P rosthetic joint infection (PJI), which occurs in 1 to 12% of surgical cases, is a common catastrophic complication of joint replacement (1-3). Hence, distinguishing PJI from other causes of joint failure, such as metal allergy or aseptic loosening, is important (4). Several tests for diagnosing PJI, including laboratory tests, nuclear medicine detection, rapid molecular tests, histopathology, and microbiologic culture (5-7), have limited sensitivity and specificity, which impedes the differentiation of PJI from other prosthetic failures (3,4,8).Sonication fluid cultures (SFC), which use sonication to dislodge bacteria from the prosthetic surface, have shown promising improvements in sensitivity compared with that for traditional tissue cultures (9). However, the sensitivities (range, 0.67 to 0.91) and specificities (range, 0.72 to 1.0) among studies assessing the diagnostic value of SFC for PJI are inconsistent (9-21). The Infectious Diseases Society of America guidelines suggest a gap in the validation of the diagnostic value of SFC for PJI and request additional higher-level evidence (8). Therefore, we evaluated the detection validity of SFC for PJI to provide further evidence for its clinical use.We searched Medline, EMBASE, and OVID for articles published between January 1990 and August 2013, using the following medical subject headings or free-text words: joint prosthesis, prosthesis infection, septic loosening, aseptic loosening, replacement, or arthroplasty; and sonication, sonicate, or ultrasonicate. We also manually searched the reference lists of eligible studies
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