Bone protection by inhibition of microRNA-182
Authors: David G Kirsch
Anil K Sood
Yufan Chen
Kazuki Inoue
Lingegowda S Mangala
Matthew B Greenblatt
Zhonghao Deng
Liang Zhao
Eugenia Giannopoulou
Gabriel Lopez-Berestein
Shiaoching Gong
Baohong Zhao
Ren Xu
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: microRNAs; therapeutic promise; skeletal diseases; osteolysis; osteoporosis
Affiliations: Arthritis and Tissue Degeneration Program, The David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, 10021, NY, USA., Department of Medicine, Weill Cornell Medical College, New York, 10065, NY, USA., Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Biological Sciences Department, New York City College of Technology, City University of New York, Brooklyn, 11201, NY, USA., Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, 10065, NY, USA., Department of Molecular Biology, The Rockefeller University, New York, 10065, NY, USA., Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA., Center for RNA Interference and Noncoding RNA, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA., Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA., Department of Radiation Oncology and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, NC, USA., Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA., Arthritis and Tissue Degeneration Program, The David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, 10021, NY, USA. ., Department of Medicine, Weill Cornell Medical College, New York, 10065, NY, USA. ., Graduate Program in Biochemistry Cell & Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, 10065, NY, USA. .

Abstract:  Targeting microRNAs recently shows significant therapeutic promise; however, such progress is underdeveloped in treatment of skeletal diseases with osteolysis, such as osteoporosis and rheumatoid arthritis (RA). Here, we identified miR-182 as a key osteoclastogenic regulator in bone homeostasis and diseases. Myeloid-specific deletion of miR-182 protects mice against excessive osteoclastogenesis and bone resorption in disease models of ovariectomy-induced osteoporosis and inflammatory arthritis. Pharmacological treatment of these diseases with miR-182 inhibitors completely suppresses pathologic bone erosion. Mechanistically, we identify protein kinase double-stranded RNA-dependent (PKR) as a new and essential miR-182 target that is a novel inhibitor of osteoclastogenesis via regulation of the endogenous interferon (IFN)-β-mediated autocrine feedback loop. The expression levels of miR-182, PKR, and IFN-β are altered in RA and are significantly correlated with the osteoclastogenic capacity of RA monocytes. Our findings reveal a previously unrecognized regulatory network mediated by miR-182-PKR-IFN-β axis in osteoclastogenesis, and highlight the therapeutic implications of miR-182 inhibition in osteoprotection. 

Retracted: No

PubPeer comments:
 Fig. 1e. Image duplication. ![file] , 
 Thank you very much for your comment. We have carefully re-checked the raw data of TRAP staining pictures for Figure 1e. We found that the image in the Mir182 inhibitor RANKL(-) condition was accidently wrongly put with the same image as in the Control RANKL(-) condition during manuscript preparation. The correct image for the Mir182 inhibitor RANKL(-) condition should be the image in the red box shown in the attached screenshot of the original pictures for Fig.1e. Unfortunately, this honest mistake was not noticed in time. We have attached the corrected Fig.1e and the screenshot of the original images here. The image in the red box is the only one that is replaced with the correct image. We apologize for this carelessness. We will contact the journal and correct this image. ![file] , 
 Thank you very much for your comment. We have carefully re-checked the raw data of TRAP staining pictures for Figure 1e. We found that the image in the Mir182 inhibitor RANKL(-) condition was accidently wrongly put with the same image as in the Control RANKL(-) condition during manuscript preparation. The correct image for the Mir182 inhibitor RANKL(-) condition should be the image in the red box shown in the attached screenshot of the original pictures for Fig.1e. Unfortunately, this honest mistake was not noticed in time. We have attached the corrected Fig.1e and the screenshot of the original images here. The image in the red box is the only one that is replaced with the correct image. We apologize for this carelessness. We will contact the journal and correct this image. ![file] , 
 Dear Authors, it has been nearly a year since this duplication was discussed - is there any word on when a correction will come out, please? In addition, could you check Supplemental Figure 11, please? The two panels marked by me with blue boxes appear to look very similar. ![file] ,