Autophagy Is Independent of the Chondroprotection Induced by Platelet-Rich Plasma Releasate
Authors: Fan Yang
Wenjing Yin
Changqing Zhang
Haoran Hu
Xuetao Xie
Ting Yuan
Guangyi Li
Journal: BioMed Research International (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Platelet-rich plasma; PRP; osteoarthritis; chondroprotection; autophagy
Affiliations: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Abstract:  Background: Platelet-rich plasma (PRP) has been shown to be a promising therapeutic agent against osteoarthritis (OA), whereas its chondroprotection mechanism is not fully elucidated. Autophagy is considered an important biological process throughout the development of OA. Therefore, the objective of the present study is to investigate the role of autophagy in the chondroprotection and compare the effects of releasate between L-PRP and P-PRP. Methods: PRP were prepared from rat blood. Rat chondrocytes pretreated in the presence or absence of interleukin-1 beta (IL-1β) were incubated with PRP releasate. The expressions of OA-related genes and autophagy-related genes were determined by RT-PCR and western blot, respectively. Autophagic bodies were assessed by transmission electron microscopy and the autophagy flux was monitored under the confocal microscopy. The effect of PRP on autophagy was further investigated in the milieu of autophagy activator, rapamycin, or autophagy inhibition by downregulation of Atg5. The effect of PRP on cartilage repair and autophagy was also evaluated in an OA rat model. Results: In vitro, PRP releasate increased the expression of the anabolic genes, COL2 and Aggrecan, and decreased the expression of the catabolic genes, whereas the expression of autophage markers, Atg5 and Beclin-1, as well as the ratio of LC3 II/LC3 I, was not significantly altered in normal or IL-1β-treated chondrocytes. Similar expression pattern was found following the activation (rapamycin) or inhibition (Atg5 silencing) of autophagy. In vivo, PRP releasate ameliorated posttraumatic cartilage degeneration while the expression of LC3 was comparable to that in the vehicle treatment group. Conclusions: PRP releasate promoted the anabolic gene expression, relieved inflammatory stress in chondrocytes, and ameliorated cartilage degeneration, but autophagy was independent of these processes. 

Retracted: No

PubPeer comments:
 Figs 12BB, 4D.  Western blot analysis of XIAP in MG63 cells 48 h after transfection with indicated plasmid ;  Western blot analysis of cleaved PARP and cleaved caspase-3 in MG63 cells after transfection with indicated plasmid. ![file] Figs 4B, 6B from [Zhang et al (2015)] . ![] Fig 4C from [Li et al (2015)] .  Western blot analysis of MMP-2 and MMP-9 protein expression after transfected with miR-338-3p mimics and corresponding negative controls. GAPDH was used as an internal control. ![] *[left]* Fig 3C from [Ge et al (2016)] .  Western blot analysis of uPA, MMP-2 and MMP-9 protein expression following transfection with miR-497 mimic or miR-control. GAPDH was used as an internal control . *[right]* Figs 3C,E from [Liu et al (2015)] .  The ... (C) protein expression levels of PTEN were detected in the HCC cells after transfection with miR-494 mimic or inhibitor. The PTEN protein expression level was detected in... (E) HCC cell lines by western blotting. ![] , 
 *[left]* Fig 6A.  Images of tumor tissue with different plasmid treatments collected after sacrifice at day 21. *[right]* Fig 6A from [Liu et al (2015)] .  Graphs of the tumor tissue from the different groups . ![file] For comparison, *[left]* Fig 7A from [Zhang et al (2015)] .  Images of tumor tissue with different groups collected after sacrifice at day 28 . *[right]* Fig 7A from [Tian et al (2015)] .  Images of tumor tissues in the different mouse groups collected after sacrifice at day 28. ![file] I have concerns. ----------------------------------------- UPDATE: Fig 5A from [Yang et al (2015)] .  Images of tumor tissue from different treatments collected after sacrifice at day 22. ![file] I have not tried to mark up the CDDP+SOR or the SOR bands, for fear of obscuring the change in texture around the 2nd tumor in the former, or the 5th tumor in the latter. , 
 *[above]* Fig 4A.  Silencing XIAP induced cell arrest and apoptosis in MG63 cells. (A) Cell DNA content distribution in each phase . *[below]* Fig 2D from [Li et al (2016)] .  ...cell cycle were determined in U2OS cells after transfected with miR-613 mimic or miR-NC . ![file] Could the authors of either paper comment on the appearance of the same panel in both? , 
 Retracted [29 October 2021] . ------------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that the western blotting data featured in Figs. 2B and 4D, the flow cytometric data in Fig. 4A and the tumour images shown in Fig. 6A were strikingly similar to data appearing in different form in other articles at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,