Gypenoside inhibits RANKL-induced osteoclastogenesis by regulating NF-Œ∫B, AKT, and MAPK signaling pathways
Authors: Yang Liu
Dongyue Su
Jiakai Han
Wei Gao
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: gypenoside(GP); osteoclast differentiation; osteoporosis; receptor activator of nuclear factor-Œ∫B ligand (RANKL).
Affiliations: Department of Endocrinology, Huaihe Hospital of Henan University, Kaifeng, Henan Province, China.

Abstract:  Gypenoside (GP) is one of the most pharmacologically active components in Gynostemma pentaphyllum and possesses neuroprotective, anticancer, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-osteoarthritis effects. However, the involvement of GP the osteoclast differentiation has not yet been investigated. In the present study, we examined the effect of GP on receptor activator of nuclear factor-Œ∫B ligand (RANKL)-induced osteoclast formation. Our results demonstrated that GP significantly inhibited the formation of osteoclast, as well as suppressed the expression of osteoclastogenesis-related marker proteins in RANKL-stimulated bone marrow macrophages (BMMs). For molecular mechanisms, GP inhibited RANKL-induced NF-Œ∫B and MAPK activation and AKT phosphorylation in BMMs. Collectively, these findings suggest that GP inhibits RANKL-induced osteoclastogenesis via regulating NF-Œ∫B, AKT, and MAPK signaling pathways. Therefore, GP may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. 

Retracted: No

PubPeer comments:
 Concerns about Figure 1: * Orange arrow: A high MW area in lane 6 B has an unexpected sharp white patch * Boxes of the same color: Some lanes appear to look very similar  , 
 Concerns about Figure 2: * Boxes of the same color: Some lanes appear to look very similar  , 
 Dr. Gupta did not yet reply here, but these blots were discussed in a recent article in The Print, where she replied. The article can be found here: https: theprint.in science icmrs-nivedita-gupta-accused-of-image-manipulation-plagiarism-in-2-papers-denies-charge 798888  Gupta has denied any manipulation of images in the work. Gupta said that the work was done while she was a PhD candidate at JNU and working at Safdarjung Hospital in 2004, and that the head of the Burns Plastic Surgery Department, R.P. Narayan, was guiding her. He is also one of the research authors and, along with her PhD guide at JNU, was privy to all raw data generated in the experiments. u201cSome of the columns that look repeated correspond to different swab samples taken from different body locations of the same patient,u201d Gupta told ThePrint. For example, in the second set of columns in the figure, the fingerprints that look identical are oral, wound, tissue biopsy and blood samples from patient number 23. u201cThis means that the Candida infection has invaded the bloodstream in burn patients, who are immunocompromised and had caused septicaemia, which is why the fingerprints are identical,u201d Gupta said. Gupta also said at the time the paper was path-breaking as it was one of the first in India to document the spread of Candida infections in the burns ward. The findings, she added, helped save many lives as doctors now know that antifungals have to be given in septicaemic burn patients when they do not respond to antibiotics. , 
 The two figures above are also included in Chapter 3 of the PhD thesis by Nivedita Gupta, as found here: https: shodhganga.inflibnet.ac.in handle 10603 15560 Another figure in that chapter is Figure 21,  RAPD analysis of C. tropicalis isolates from different patients except 60 and 90. Some of the bands there appear to be surrounded by rectangular boxes with a sharp background transition, as marked here with red arrows.  Figures 24 and 25 in that thesis chapter show C. albicans strains from burn patients where Pseudomonas was or was not isolated from the burn wound. As shown by boxes of the same color, several of these photos appear to look more similar than expected.  , 
 Chapter 1, the introduction to the PhD thesis by Nivedita Gupta, contains paragraphs that contain verbatim or nearly verbatim sentences from text published by others. In particular, text from the book *Fungal Pathogenesis: Principles and Clinical Applications* (2002) by Richard A Calderone (eBook ISBN 9780429153228) appears to have been copied. For example, here is text from Chapter 30 in that book, written by Derek J Sullivan and David C Coleman (left), and text in Section 1.4.2 from the Gupta PhD thesis (right). Boxes of the same color show blocks of texts that are remarkably similar.  And here is text from Chapter 26 in that book (left), and text in Section 1.6.3 from the Gupta PhD thesis (right).  I did not investigate other sections in detail. ,