Knockdown of ADAM10 inhibits migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Xianji Song
Zhitao Xiao
Gang Wang
Dan Li
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Rheumatoid arthritis; ADAM10; inflammation; arthritis; fibroblast-like synoviocytes
Affiliations: Department of Radiology, The First Teaching Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Department of Engineering Mechanics, Jilin University, Changchun, Jilin 130021, P.R. China., Department of Orthopaedics, The Third Teaching Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Abstract:  Rheumatoid arthritis (RA) is a systemic autoimmune disease with high rates of morbidity and mortality. Previous studies proposed that the A disintegrin and metalloprotease (ADAM) family is involved in the regulation of inflammation and arthritis. Thus, the present study investigated whether ADAM10 is involved in the progression of RA. The effects of ADAM10 small interfering (si)RNA on the expression levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑8 and chemokine (C-X-C motif) ligand 16 (CXCL16) were determined in fibroblast‑like synoviocytes (FLS). In addition, the effects of ADAM10 siRNA on cell proliferation, invasion and migration in human RA‑FLS were assessed in vitro. The therapeutic efficacy and side‑effects of ADAM10 siRNA were examined in a mouse model of collagen‑induced arthritis (CIA). In vitro, ADAM10 silencing suppressed the expression of TNF‑α, IL‑6, IL‑8 and CXCL16 in lipopolysaccharide (LPS)‑stimulated human RA‑FLS. LPS‑induced RA‑FLS proliferation, migration and invasion were significantly attenuated by ADAM10 knockdown. ADAM10 silencing inhibited the secretion of vascular endothelial growth factor A (VEGF‑A) and matrix metalloproteinase (MMP)‑3 and ‑9 from LPS‑stimulated human RA‑FLS, in addition to inhibiting the phosphoinositide 3‑kinase/AKT activation in LPS‑stimulated human RA‑FLS. In vivo, treatment with siRNA against ADAM10 for three weeks reduced the arthritis score. Serum levels of VEGF‑A, MMP‑3 and MMP‑9 were also reduced in CIA mice. These observations indicate that the inhibition of ADAM10 may be a viable therapeutic target in the amelioration of disease progression in RA by attenuating FLS proliferation, migration and invasion. 

Retracted: Yes

PubPeer comments:
 The values presented in Table 1 are hard to believe. ![file] , 
 Since this problem has not been addressed, I can add some more for you to chew on: Many of the numbers in Table 1 also appear in Table 1 in another paper (Devadatha B et al., 2020, Microb Pathol). ![file] , 
 Dear Indigofera Tanganyikensis Find the raw data. Kindly try to understand about the preliminary screening of samples and observe the results from the literature. We don t find any error in our raw data. , 
 #3 I don t see raw data. #1, #2 The table makes sense when one assumes that three measurements per data-point where taken and that the outcome of each measurement was an integer number (inhibition recorded in whole milimeters). E.g. the oft-repeating 8.33+-0.57 then is the outcome of three measurements yielding 8, 8, and 9 (8.33333... mean, 0.5774... SD, with rounding error in the reported SD). 8+-0 could be 8, 8, 8. 10.33+-0.57 could be 10, 10, 11. 11. 11+-1 could be 10, 11, 12. Anyway, when doing only 3 measurements that yield a discrete, limited number of outcomes one can expect repeats. I could not reconstruct all calculations, e.g. 11.67+-1.52 has no clear solution. 10,11,14 gives SD of 2.1; 11,11,13 an SD of 1.2. Trying 0.5 mm steps, e.g. 10.5, 11, 13.5 also gives no match (SD 1.6). The exclusive .00 , 0.33 , and 0.67 endings make clear that the authors really went for the average of three measurements in rounded mm units. And this specific combination does not seem possible. Note that there are automatic tools to test this . This may elucidate whether the 11.67+-1.52 and others are reasonable. And the raw data would help, obviously. Note that I know nothing on content, e.g. whether it is reasonable to only measure the inhibition for 3 colonies. , 
 Test is Sprite , available online as http: www.prepubmed.org sprite. 11.67+-1.52 is 10, 12, 13 with an SD of 1.5275... rounded wrongly to 1.52. The authors are mostly careless with rounding, reporting the means of the 2nd row to 1 decimal place (16.30 versus 16.33) but rounding the standard deviation of 1.5275... correctly up to 1.53. In other place the SD is truncated to 1.52, or a .6666.. average is truncated to .66 . ,