Proepithelin stimulates growth plate chondrogenesis via nuclear factor-kappaB-p65-dependent mechanisms
Authors: Shufang Wu
Hongzhi Sun
Xu Li
Weijin Zang
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Proepithelin; cartilage formation; cell proliferation; differentiation; apoptosis
Affiliations: First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School of Xi'an Jiaotong University, Xi'an, 710061 China. 

Abstract:  Proepithelin, a previously unrecognized growth factor in cartilage, has recently emerged as an important regulator for cartilage formation and function. In the present study, we provide several lines of evidences in proepithelin-mediated induction of cell proliferation, differentiation, and apoptosis in the metatarsal growth plate. Proepithelin-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by pyrrolidine dithiocarbamate, a known NF-κB inhibitor. In rat growth plate chondrocytes, proepithelin induced NF-κB-p65 nuclear translocation, and nuclear NF-κB-p65 initiated its target gene cyclin D1 to regulate chondrocyte functions. The inhibition of NF-κB-p65 expression and activity (by p65 short interfering RNA (siRNA) and pyrrolidine dithiocarbamate, respectively) in chondrocytes reversed the proepithelin-mediated induction of cell proliferation and differentiation and the proepithelin-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of proepithelin on NF-κB activation. Finally, using siRNA and antisense strategies, we demonstrated that endogenously produced proepithelin by chondrocytes is important for chondrocyte growth in serum-deprived conditions. These results support the hypothesis that the induction of NF-κB activity of in growth plate chondrocytes is critical in proepithelin-mediated growth plate chondrogenesis and longitudinal bone growth. 

Retracted: Yes

PubPeer comments:
 Sent to me by a reader. Figure 6B: unexpected similarities between the 12h Cytoplasmic Lamin B lane and the 0h Nuclear GAPDH lane, so between blots that represent different cell fractions, time points, and immunoblots. Highlighted with red boxes. Contrast adjusted to bring out more details. ![file] , 
 2020 retraction. https: www.jbc.org content 295 26 8874 This article has been withdrawn by the authors. The authors were recently made aware that in Fig. 6B, the cytoplasmic p65 lane at 12 h was reused as the nuclear Lamin B lane at 12 h, flipped horizontally. The cytoplasmic Lamin B lane at 12 h was reused as the nuclear GAPDH lane at 0 h. In Fig. 7A, the third lane in the Proepithelin immunoblot appeared to be spliced. The authors affirm that all experiments were performed appropriately, and they state that experimental data generated in the laboratory from the same time period support the original conclusions of the study. The authors state that these issues do not affect the accuracy of the overall results or the conclusions of the scientific work. However, in the interest of maintaining the accuracy in the published scientific literature, the authors wish to withdraw this article and will seek to publish a new version of the article corroborating the findings of this work in the future. , 
 Assessed here, as part of the third of 10 broad investigations: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- **Decision on the handling of problems such as improper image manipulation, confusion of experimental data, and false information in project applications published by Wu Shufang, Zhou Bo, etc.** - National Science and Technology Financial Supervisory Office [2022] No. 11 u3000u3000The Supervision Committee of the National Natural Science Foundation of China launched an investigation into the papers published by Wu Shufang and Zhou Bo of Xi an Jiaotong University for suspected academic misconduct. The papers involved are as follows: ... u3000u3000Paper 2:  Shufang Wu, Weijin Zang, Xu Li, Hongzhi Sun*. **Proepithelin Stimulates Growth Plate Chondrogenesis via Nuclear Factor B-p65-dependent Mechanisms**. J Biol Chem, 2011, 286(27): 24057-24067. Fund No. 30930105, 30971392, 81071440) ... u3000u3000After investigation, papers 1, 2, and 3 have problems such as improper operation of pictures and confusion of experimental data, and the first author Wu Shufang is mainly responsible. In addition, Wu Shufang listed 3 papers in her application for the National Natural Science Foundation of China (approval numbers 81071440, 81222026, 81472038, 81672221, 81871813) for many times, and she is also responsible for the objective results of false information in the project application; Papers 4 and 5 have problems such as improper operation of pictures and confusion of experimental data. Zhou Bo (the corresponding author of paper 4 and the first author of paper 5) is mainly responsible. In addition, Zhou Bo listed Paper 4 in his final report of the National Natural Science Foundation of China (Grant No. 81500016), and listed Paper 5 in his application for the National Natural Science Foundation of China (Grant No. 81500016), and should also be included in the project application Responsible for the objective results of false information in the book and final report. u3000u3000After deliberation at the 12th meeting of the Fifth National Natural Science Foundation of Item 2 of Article 16 and Item 3 of Article 17,  Measures for Handling Misconduct in Funding Work (for Trial Implementation) , and the revocation of the Wu Shufang National Natural Science Foundation project  FGF21 Mediates  Growth Hormone Insensitivity Cartilage Development  Research on the mechanism of retardation (Grant No. 81071440),  Research on the mechanism of autophagy regulation in cartilage dysfunction-related diseases (Grant No. 81222026),  Research on the mechanism of abnormal cartilage function in the state of growth hormone insensitivity due to peripheral circadian clock disorders (Approval No. 81472038),  Study on the regulation mechanism of Sirt1 on endochondral osteogenesis and maintenance of cartilage homeostasis (Approval No. 81672221),  Study on the direct effect and mechanism of peripheral neurotransmitter NPY in cartilage degeneration (Approval No. 81871813 ), recover the funds allocated for the above 5 projects, cancel Wu Shufangu2019s application qualification for the National Natural Science Foundation of China for 3 years (January 18, 2022 to January 17, 2025), and give Wu Shufang a notice of criticism; Item 4 of Article 35 of the Regulations of the Natural Science Foundation of China, Item 2 of Article 16 and Article 17 of the Measures for Handling Misconduct in the Funding Work of the National Natural Science Foundation of China (for Trial Implementation) The third item is to cancel the Zhou Bo National Natural Science Foundation project  Research on the regulatory mechanism of autophagy in the improvement of airway inflammation in bronchial asthma by chemical partners (Grant No. 81500016), recover the allocated funds, and cancel the Zhou Bo National Natural Science Foundation project Eligibility to apply for 2 years (January 18, 2022 to January 17, 2024), give Zhou Bo a bulletin for criticism. - National Natural Science Foundation of China - March 30, 2022 ,