A disintegrin and metallproteinase 15 knockout decreases migration of fibroblast-like synoviocytes and inflammation in rheumatoid arthritis
Authors: Liming Wang
Bailin Song
Wei Zheng
Jinliang Gao
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: ADAM15; inflammatory conditions; cell migration; fibroblast-like synoviocytes; rheumatoid arthritis
Affiliations: Department of Rheumatism, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China., Department of Ophthalmology, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China., Department of Otolaryngology, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China., Department of Massage, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China.

Abstract:  The aim of the present study was to determine whether the expression of A disintegrin and metallproteinase 15 (ADAM15) affected the inflammatory conditions and cell migration in human fibroblast‑like synoviocytes (FLSs) in a rat model of rheumatoid arthritis (RA). The expression of ADAM15 in FLSs stimulated with lipopolysaccharide (LPS) was confirmed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The effects of small interfering RNA targeting ADAM15 (siADAM5) on pro‑inflammatory cytokines and chemokines were assessed using an enzyme‑linked immunosorbent assay. The effects of siADAM15 on cell invasion and migration in FLS were also assessed in vitro. The therapeutic effects and side effects of ADAM15 in a rat model of collagen‑induced arthritis (CIA) were examined in vivo. The present results revealed that ADAM15 expression was significantly elevated at the mRNA and protein level in FLSs stimulated with LPS and that silencing ADAM15 suppressed the expression of pro‑inflammatory cytokines and chemokines, preventing FLS cell migration and invasion via inhibiting vascular endothelial growth factor‑A, matrix metalloproteinase (MMP)1 and MMP‑3 expression. In addition, treatment of CIA rats using siADAM15 significantly reduced the arthritis score and extent of joint damage in the rats. These findings indicated that silencing ADAM15 had anti‑inflammatory effects in FLSs and efficiently inhibited the development of CIA. Therefore, ADAM15 may be a potential target molecule for RA therapies. 

Retracted: No

PubPeer comments:
 Fig 1B.  Following stimulation with LPS, ADAM15 protein was evaluated using western blotting . ![file] Pink and red boxes mark two lanes of the ADAM15 band, flipped horizontally to heighten the similarity to Fig 5C, [Li et al (2014)] . Note also the similarity of the loading-control bands (green boxes). ![file] , 
 Fig 5A.  FLSs were pretreated with siADAM15 for 24 h and exposed to human LPS for 48 h. VEGF-A, MMP-3 and MMP-9 protein expression were measured using western blotting. ![file] MMP-3 band flipped by 180 deg to heighten similarity of lanes marked with orange and brown boxes to Figs 3C and 7 from [Liu et al (2014)] . ![] Multiple other manifestations of the band are linked in that thread. ,