PMID- 23178792 OWN - NLM STAT- MEDLINE DCOM- 20130620 LR - 20211021 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 62 IP - 2 DP - 2013 Feb TI - Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid arthritis. PG - 229-37 LID - 10.1007/s00011-012-0572-1 [doi] AB - OBJECTIVE: Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients. METHODS: Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman's correlation analysis. RESULTS: In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = -0.8937). CONCLUSION: The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a. FAU - Xu, Ke AU - Xu K AD - Department of Joint Surgery, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China. FAU - Xu, Peng AU - Xu P FAU - Yao, Jian-Feng AU - Yao JF FAU - Zhang, Yin-Gang AU - Zhang YG FAU - Hou, Wei-Kun AU - Hou WK FAU - Lu, She-Min AU - Lu SM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121120 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BECN1 protein, human) RN - 0 (Beclin-1) RN - 0 (MAP1LC3A protein, human) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) RN - 0 (Microtubule-Associated Proteins) SB - IM MH - Adult MH - Aged MH - *Apoptosis MH - Apoptosis Regulatory Proteins/metabolism MH - Arthritis, Rheumatoid/*metabolism MH - *Autophagy MH - Beclin-1 MH - Female MH - Humans MH - Male MH - Membrane Proteins/metabolism MH - MicroRNAs/genetics MH - Microtubule-Associated Proteins/metabolism MH - Middle Aged MH - Synovial Membrane/*metabolism EDAT- 2012/11/28 06:00 MHDA- 2013/06/21 06:00 CRDT- 2012/11/27 06:00 PHST- 2012/04/12 00:00 [received] PHST- 2012/10/25 00:00 [accepted] PHST- 2012/10/15 00:00 [revised] PHST- 2012/11/27 06:00 [entrez] PHST- 2012/11/28 06:00 [pubmed] PHST- 2013/06/21 06:00 [medline] AID - 10.1007/s00011-012-0572-1 [doi] PST - ppublish SO - Inflamm Res. 2013 Feb;62(2):229-37. doi: 10.1007/s00011-012-0572-1. Epub 2012 Nov 20.