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low, study results were pooled per factor. If pooling was considered not appropriate a best evidence synthesis was conducted. The best evidence synthesis was conducted as follows: associations were categorized as positive, negative or no association. The ranking of levels of evidence was formulated as 1. Strong evidence: consistent finding ( 75% of the studies showing the same association) in multiple studies with a low risk of bias in all domains of the QUIPS tool, 2. Moderate evidence: consistent findings (75% of the studies showing the same association) in multiple studies with a moderate of high risk of bias in one or more domains of the QUIPS tool, 3. Limited evidence: one study with a low risk of bias in all domains of the QUIPS tool or 2 studies with moderate of high risk of bias in one or more domains of the QUIPS tool, 4. Conflicting evidence: <75% of the studies showing the same association, 5. No evidence: No studies found. Results: We included 56 different articles, describing 147 different factors. Three studies were assessed as low risk of bias in all domains of the QUIPS tool. Seventy-nine factors were reported once (one study). The clinical heterogeneity of the studies describing the other 68 factors (reported more than once) was considered too large to conduct a metaanalysis. Therefore we conducted a best evidence synthesis, separately for each factor regarding clinical progression (C), radiological progression (R) or progression to THR (T). No strong evidence was found for any prognostic factor. Moderate evidence was found for more or faster progression in patients having comorbidity (C), a family history of OA (R), more pain at baseline (T), a lower global assessment reported by the patient at baseline (T), certain modes created by statistical shape modelling (T) and a higher K-L grade at baseline (T).

and, in addition to its powerful antioxidant activity, it may exert modulatory effects on different signalling pathways. Methods: The immortalized human cell line C-28/I2 and primary cultures of human chondrocytes (prepared from fragments of articular cartilage obtained from adult OA patients undergoing knee arthroplasty) were treated with HT, 30 minutes before exposition to hydrogen peroxide to induce oxidative stress and samples were collected at different times. We tested cell viability through reading on MUSE Ò Cell Analyzer. The expression of genes and proteins known or potentially implicated in OA was evaluated by Real-Time RT-PCR assay and by Western blot method, respectively. By 6 different algorithms (TargetScan, miRanda, PICTAR4, miRDB, miRWalk, RNA22) bioinformatic analysis selected possible candidate microRNAs that could interact with targets of interest. Subsequently we verified by Real Time RT-PCR assay possible variations in the expression of these microRNAs after treatments. Results: We evaluated the gene expression of runt-related transcription factor-2 and matrix metalloproteinase-13, two molecular markers of OA, in human primary chondrocytes cultured in monolayer. HT prevents the increase induced by oxidative stress in the mRNA amount of both markers. Moreover this compound is able to reduce significantly C-28/I2 cells death. In order to investigate a possible involvement of autophagic process in this context, we evaluated the protein expression of LC3 II (active form associated to autophagosomes), after oxidative stress in presence or in absence of HT. We found that HT induces an increase of protein levels of this autophagic marker, suggesting a possible mechanism of cytoprotection. This effect of HT on autophagy may be promoted by modulating several effectors such as AMP-activated protein kinase (AMPK) and the NAD-dependent deacetylase Sirtuin-1 (SIRT-1). Indeed HT causes the increase of phospho-AMPK and SIRT-1 protein levels. At the same time, this compound is able to decrease the amount of microRNA-9, which can target SIRT-1 mRNA thus modulating its expression. Conclusions:This study suggests new molecular mechanisms by which HT may prevent some aspects of OA pathogenesis and progression. Indeed the beneficial action of HT in this context seems to be related to the stimulation of autophagy. These data indicate that HT can be considered an attractive tool for the prevention of OA.This work was supported by FIRB (Ministero dell'istruzione, dell'Universit a e della Ricerca, Italy) grant RBAP10KCNS.