A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity
Authors: Yutong Dong
Yueqi Chen
Yong Tang
Wenhui Hu
Haibo Li
Ye Wei
Xiaoming Li
Yiran Wang
Lincheng Zhang
Shiwu Dong
Yuheng Li
Xiaochao Yang
Journal: Clinical and Translational Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: PTEN; inflammatory osteolysis; osteoclastogenesis; small molecule.
Affiliations: Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, PR China., Department of Orthopaedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, PR China., National Engineering Research Center of Immunological Products & Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing, PR China., School of Chemistry and Chemical Engineering, Southwest University, Chongqing, PR China., State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, PR China.

Abstract:  Background: Inflammatory osteolysis is a severe infectious bone disorder that occurs during orthopaedic surgery and is caused by disruptions in the dynamic balance of bone matrix homeostasis, which makes this condition a burden on surgical procedures. Developing novel therapeutic drugs about inhibiting excessive osteoclastogenesis acts as an efficient approach to preventing inflammatory bone destruction. Methods: To study this, we explored the potential effects and mechanisms of compound 17 on inflammatory osteolysis in vitro. Meanwhile, a lipopolysaccharide (LPS)-induced calvarial osteolysis mouse model was used to evaluate the protective effect of compound 17 on inflammatory bone destruction in vivo. Results: In our study, we found that compound 17 could inhibit osteoclast (OC) differentiation and bone resorption during RANKL and LPS stimulation in a time- and dose-dependent manner, while compounds 5 and 13 did not have the same effects. Mechanistically, compound 17 promoted phosphatase and tensin homologue (PTEN) activity by reducing PTEN ubiquitination, thereby restraining the RANKL-induced NF-κB pathway, resulting in the inhibition of the expression of osteoclastogenesis-related genes and the formation of the NLRP3 inflammasome. Additionally, we also investigated whether compound 17 could negatively modulate macrophage polarization and repolarization due to its anti-inflammatory effects. Moreover, compound 17 also plays an important role in osteoblast differentiation and mineralization. In vivo experiments showed that compound 17 could effectively protect mice from LPS-induced inflammatory bone destruction by inhibiting osteoclastogenesis and inflammation. Conclusions: Taken together, these results show that compound 17 might play protective role in inflammatory bone destruction through inhibiting osteoclastogenesis and inflammation. These findings imply a possible role of compound 17 in inflammatory osteolysis-related diseases. 

Retracted: No

PubPeer comments:
 Second author here, Stepan Nikolaevich Morozov, is assigned an affiliation to  Faculty of Mathematics and Mechanics, St. Petersburg State University, Russia . No-one of that name is listed at the [Mathematics Mechanics Faculty website] . Nor has anyone of that name published any papers other than this one. Could the other authors check whether he exists? Authors Chen Chen do have prior form for [inventing or identity-stealing co-authors] . , 
 **Forged affiliation of the corresponding author** The affiliation of the author C.Y.J. Chen to _NAAM Research Group, King Abdulaziz University_ Saudi Arabia, is erroneous and abusive. This university never employed C.Y.J. Chen between 2018 and 2021. The author C.Y.J. Chen, alias J.C.Y. or John Chen, exhibited 29 different academic affiliations in different institutes and or universities in 15 different countries (i.e. Bangladesh, Nigeria, Saudi Arabia, United States, Papua New Guinea, Taiwan, United Kingdom, Brasilia, Australia, China, Russia, Kazakhstan, Vietnam, Spain, Egypt) for the 68 articles (minimum) published between 2018 and 2021, in which he is a co-author with Tim Chen (timchen@tdtu.edu.vn). In this paper, the corresponding author used two email addresses: his  usual one, jc343965@gmail.com, and also Tim Chen s address: timchen@tdtu.edu.vn, who was affiliated to the Ton Duc Thang University in Vietnam. **References** Three references with **Cheng-Wu Chen** as a first author were quoted in this section: 1. Chen, C.-W., Lee, C.-C., Chen, C.-H., Tseng, C.-P. 2013a. The integration of nautical hazard assessment and harbor GIS models to the Taichung Port area in Taiwan. Nat Hazards. 67(2):275-94. 2. Chen, C.-W., Liu, K.F.-R., Lin, M.-L., Tseng, C.-P. 2013b. A new viewpoint of hazard assessment and management for Taiwan s insurance issues. Nat Hazards. 65(1):303-14. 3. Chen, C.-W., Liu, K.F.-R., Tseng, C.-P., Hsu, W.-K., Chiang, W.-L. 2012. Hazard management and risk design by optimal statistical analysis. Nat Hazards. 64(2):1707-16. PubPeer comments were already posted for [other papers] written by the author Cheng-Wu Chen and still published in the journal _Natural Hazards_. It is likely that Tim Chen or C.Y.J. Chen is none other than [Cheng-Wu Chen] or his twin-brother [Chen-Yuan Chen] . ,