Adipose‐derived mesenchymal stromal cells suppress osteoclastogenesis and bone erosion in collagen‐induced arthritis
Authors: Ji-Nan Wei
Rui Geng
Qing Chang
Yunjie Lu
Chao Li
Jun-Zheng Hu
Journal: Scandinavian Journal of Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: cells; cytokines; inflammation; molecules; processes
Affiliations: Department of Orthopaedics Zhongda Hospital Medical School Southeast University Nanjing China, The First People's Hospital of Changzhou the Third Hospital Affiliated to Soochow University Changzhou China

Abstract:  Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA), and adipose-derived mesenchymal stromal cells (ADSCs) can inhibit experimental collagen-induced arthritis model. This study aims to determine whether ADSCs also suppresses osteoclastogenesis and bone erosion in collagen-induced arthritis (CIA). Osteoclasts were induced from bone marrow-derived CD11b+ cells with receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) stimulation and assessed with tartrate-resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were produced from human CD14+ cells. ADSCs were generated and added to cultures with different ratios with CD11b+ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF-κB and RANKL expression were determined by Western blotting and RT-qPCR. About 2 × 106 ADSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with type II collagen/complete Freund's adjuvant (CII/CFA) while the onset and severity of the CIA were monitored. Adipose-derived mesenchymal stromal cells but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice. ADSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with ADSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. We have demonstrated that ADSCs can inhibit RANKL-induced osteoclasts genesis via CD39 signals. Our findings also suggest that ADSCs can inhibit osteoclasts genesis without the involvement of regulatory T cells. ADSCs might represent a promising strategy for stem cell-based therapies for RA. Thus, manipulation of ADSCs may have therapeutic effects on RA and other bone erosion-related diseases. 

Retracted: No

PubPeer comments:
 Corrigendum, January 2021, found here: https: onlinelibrary.wiley.com doi 10.1111 sji.13015  In this article,1 there is an error in Figure 3A on page 6. The correct figure is shown below: [...] Also, the following funding information has been removed. National Natural Science Foundation of China, Grant Award Number: 81971504. The authors apologize for the errors. , 
 Here is the original Figure 3A, where the Fibroblast panel appears to overlap with figure panels in another paper by some of the same authors, i.e. Han Sun et al., Immunity Inflammation and Disease (2020), doi: 10.1002 iid3.364 - https: pubpeer.com publications 124D233BDBB0BCC3292231081AB144 In that paper two figure panels in Figure 1A have a tiny overlap with each other, and both overlap with the Fibroblast panel in Figure 3A. The animal models appear to be different. ![file] ![file] , 
 Not addressed in the Corrigendum is a possible overlap between two panels in Figure 5A, marked here with red boxes: ![file] , 
 We are so sorry for the mismatched image in Figure 5A. This is our mistake in interpreting the figures in the manuscript, which might use the mismatched images in 3A and 5A. Now we are providing the corrected figure for figure 5A to the editor. Besides, we have also provided two separate and repeated data for the editor s investigation. It does not affect the scientific results we made in the paper. The mistake is a careless mistake as we mixed the data in the wrong group. We are very sorry and will deeply examine our mistake and correct our attitude in future scientific research. ,