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Background/aim This study aims to identify the role of synovial fluid levels of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) for the prediction of intraarticular steroid injection success in knee osteoarthritis (OA). Material and methods A total of eighty-four advanced stage knee OA patients (42 with stage 3 OA and 42 with stage 4 OA) were enrolled in the study. Baseline and posttreatment outcomes were determined using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pretreatment synovial fluid ADAMTS9 and ADAMTS4 levels were measured by enzyme linked immunosorbent assay (ELISA). ‘’Total WOMAC score regression of 18% and above’’ was taken as a minimal clinically important difference (MCID) to indicate improvement. Determining the best predictors of intraarticular steroid injection success in both groups was evaluated by multiple logistic regression analyses. Results Synovial fluid ADAMTS9 levels were significantly lower in the stage 4 OA group when compared with the stage 3 group. The level of synovial fluid ADAMTS9 was statistically significantly lower in the WOMAC score percent change ≥18% than the WOMAC score percent change

Maximum lifespan varies by two orders of magnitude across mammals. How such divergent lifespans have evolved remains an open question, with ramifications that may potentially lead to therapies for age-related diseases in humans. Several species of microbats as well as the naked mole-rat live much longer than expected given their small sizes, show reduced susceptibility to neoplasia, and largely remain healthy and reproductively capable throughout the majority of their extended lifespans. The convergent evolution of extreme longevity in these two groups allows for the opportunity to identify potentially important aging related genes that have undergone adaptive sequence convergence in these long-lived, yet small-bodied species. Here, we have tested 4,628 genes for evidence of convergence between the microbats and naked mole-rat. We find a strong signal of adaptive sequence convergence in the gene A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 9 (ADAMTS9). We also provide evidence that the shared substitutions were driven by selection. Intriguingly, ADAMTS9 is a known inhibitor of the mTor pathway and has been implicated in several aging related processes.

Objective: Recent studies performed in the central nervous system highlight the pathophysiological relevance of A disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) genes and their protein products. The determination of alterations in expression profiles of ADAMTS family genes in Alzheimer’s disease (AD) patients may contribute to the explanation of tissue pathology and also new ideas for remedial approaches for this incurable but preventable disease. Therefore, the goal of this study was to describe and identify the distribution, characteristics, and any changes in the expression, in other words, immunoreactivity, for aggrecanases (ADAMTS4, 5, 9, and 15) proteins in AD brain. Methods: Nine cases that were autopsied in the Council of Forensic Medicine, Bursa Morgue Department in 2013, were selected. All of the cases were sent for autopsy to the institution within 8 hours after death. At autopsy, tissue samples were obtained for histopathological examination of organs for determining the cause of death. Out of these, two cases were diagnosed with AD by neurologists when they were alive. Immunohistochemical staining was performed on the brain slides by using relevant primary and secondary antibodies against aggrecanase proteins. All images were acquired using a X200 objective of a microscope (Olympus BX53) and evaluated by the staining intensity using a semi-quantitative scoring system. Results: ADAMTS4 and 5 were slightly under-expressed in the brains from autopsied AD cases compared to those of control brains and suggested that extracellular matrix (ECM) degradation was not endorsed in AD brain. On the other hand, ADAMTS9 and 15 aggrecanases were not found to be expressed in correspondent brain sections of AD and control cases. Conclusion: The current study demonstrated that some aggrecanases were found to be under-expressed in AD brains. Additional studies in which all ADAMTS enzymes will be studied in terms of mRNA and protein levels are needed to understand the relative contributions of ADAMTS genes and proteins in AD brains.

Chromosome region 3p12‐14 is an important tumour suppressor gene (TSG) locus for multiple cancers. ADAMTS9, a member of the metalloprotease large family, has been identified as a candidate 3p14.2 TSG inactivated by aberrant promoter CpG methylation in several carcinomas, but little known about its expression and function in breast cancer. In this report, ADAMTS9 expression and methylation was analysed in breast cancer cell lines and tissue samples. ADAMTS9 RNA was significantly down‐regulated in breast cancer cell lines (6/8). After treating the cells with demethylation agent Aza and TSA,ADAMTS9 expression was dramatically increased. Bisulphite genomic sequencing and methylation‐specific PCR detected promoter methylation, which was associated with decreased ADAMTS9 expression. Hypermethylation was also detected in 130/219 (59.4%) of primary tumours but only in 4.5% (2/44) of paired surgical margin tissues. Ectopic expression of ADAMTS9 in tumor cells induced significant growth suppression, cell cycle arrest at the G0/G1 phase, enhanced apoptosis and reduced cell migration and invasion. Conditioned culture medium from ADAMTS9‐transfected BT549 cells markedly disrupted tube formation ability of human umbilical vein endothelial cell (HUVEC) in Matrigel. Furthermore, ADAMTS9 inhibited AKT signaling and its downstream targets (MDM2, p53, p21, p27, E‐cadherin, VIM, SNAIL, VEGFA, NFκB‐p65 and MMP2). In addition, we demonstrated, for the first time, that ADAMTS9 inhibits AKT signaling, through suppressing its upstream activators EGFR and TGFβ1/TβR(I/II) in breast cancer cells. Our results suggest that ADAMTS9 is a TSG epigenetically inactivated in breast cancer, which functions through blocking EGFR‐ and TGFβ1/TβR(I/II)‐activated AKT signaling.