Osteoarthritis (OA) is a major public health concern for which a reliable non-invasive treatment option has yet to be developed. In the present study, we investigated the effects of saxagliptin, a novel dipeptidyl peptidase IV (DPP-4) inhibitor, on several important aspects of the pathophysiology of OA using primary human chondrocytes. The results of real-time PCR and ELISA analyses show that saxagliptin treatment significantly decreased mRNA and protein expression of three key cartilage degrading enzymes: matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. The results of western blot confirmed that this decrease in MMP-1, -3, and -13 expression prevented degradation of type II collagen. We also found that saxagliptin significantly inhibited expression of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4 and ADAMTS-5, which was reflected by markedly decreased degradation of aggrecan. Inhibition of DPP-4 by saxagliptin also reduced oxidative stress in human primary chondrocytes as evidenced by decreased production of reactive oxygen species (ROS) and increased glutathione (GSH) levels. Additionally, the results of western blot analysis show that the effects of saxagliptin are mediated through the p38/IjBa/NF-jB pathway, which is considered an important treatment target for OA. These findings suggest a potential role for saxagliptin as a novel treatment against OA.
Purpose To describe the bilateral coracohumeral morphological discrepancy in rotator cuf rupture patients with and without subscapularis (SSC) involvement and to investigate its association with SSC tears. Methods Two hundred and thirteen consecutive patients who were scheduled to have arthroscopic rotator cuf repair were prospectively enrolled in the current study. Patients with acute traumatic rotator cuf rupture, glenohumeral osteoarthritis, bilateral rotator cuf rupture, recurrent shoulder instability, systemic inlammatory disease, and previous shoulder surgery history were excluded. Coracohumeral distance (CHD), coracoid overlap (CO), lesser tuberosity index (LTI) and acromiohumeral interval (AHI) were measured bilaterally using CT scans. Based on arthroscopic indings, patients were included in either the SSC tear group (n = 72) or the control group (n = 141).
ResultsIn the SSC tear group, the afected shoulder possessed a signiicantly smaller CHD [95% conidence interval (CI) 6.1-7.2 vs. 7.2-8.0 mm, p < 0.0001], larger LTI (95% CI 9.4-9.9 vs. 9.0-9.6 mm, p < 0.0001), and smaller AHI (95% CI 5.0-5.5 vs. 7.1-7.5 mm, p < 0.0001) than the contralateral normal shoulder. In the control group, there was no signiicant diference between bilateral CHD and CO, and the AHI bilateral discrepancy was less distinct. CO did not difer signiicantly in the bilateral comparison in either group. Among all evaluated parameters, bilateral CHD discrepancy was the best predictor of SSC tears, with an area under the curve (AUC) of 0.882. A cutof value of 0.5 mm had a sensitivity of 76.4% and speciicity of 99.3% for SSC tears.
ConclusionThe CHD values are signiicantly diferent between afected and contralateral shoulders in SSC tear patients. Bilateral CHD discrepancy is closely associated with subcoracoid impingement and SSC tears, and its presence warrants speciic intraoperative SSC inspection. Level of evidence Level II.
Skeletal metabolic homeostasis integrity is sustained and orchestrated by osteoclast interceded bone resorption and osteoblast interceded bone formation. 1 An increase in osteoclast formation contributes to excessive bone remodelling and thus induces many osteolytic problems, including osteoporosis, 2 aseptic loosening of prostheses, 3 inflammatory osteolysis, 4 rheumatoid arthritis 5 and metastatic cancers. 6 Among them, inflammatory osteolysis, characterized by excessive bone mass loss, is mainly attributed to bacterial
Purpose The study purpose is to characterize the sizes of the anterior cruciate ligament (ACL) insertion site and intercondylar notch in Chinese patients undergoing ACL surgery. The findings will provide a reference for individualized clinical treatment of ACL rupture. Methods For this study, 137 patients (102 males, 35 females) with an average age of 30.3 ± 9.5 years (range 14-52 years) undergoing ACL reconstruction were included. The tibial ACL insertion site length and width and the intercondylar notch width were measured on MRI and arthroscopically using a ruler. Descriptive statistics of the patients, the distribution of the measurements and the differences between males and females were calculated. Results The ACL tibial insertion size and intercondylar notch width in Chinese patients with ACL injuries, as obtained by MRI and intra-operatively, exhibited significant individual variability. The tibial ACL insertion site had a mean length of 13.5 ± 2.1 mm and width of 10.9 ± 1.5 mm as measured on MRI and a mean length of 13.3 ± 2.1 mm and width of 11.0 ± 1.6 mm as measured intra-operatively. The mean intercondylar notch width was 15.2 ± 2.4 mm on MRI and the mean length was 15.0 ± 2.5 mm intra-operatively. The inter-rater reliability between MRI and intra-operative measurements confirmed that the two methods were consistent. In 65.7% of individuals, the ACL tibial insertion length was < 14 mm. Conclusion The distribution of tibial footprint size in Chinese patients is different from that in Western populations. There is a higher proportion of subjects with a tibial footprint size < 14 mm among Chinese patients with ACL injury. Therefore, great care should be taken when treating this population with the double-bundle technique or larger graft options. Level of evidence IV.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.