Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation
Authors: Hong Chen
Nian Zhou
Wei Xu
Tingxu Fan
Junyi Liao
Qiang Cheng
Shixiong Yi
Zhong Yang
Cheng Chen
Wei Bao
Chen Zhao
Yongming Zeng
Xi Liang
Liangbo Lin
Weike Si
Ning Hu
Wei Huang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Bone morphogenetic protein 2 (BMP2); chondrogenic growth factors; cartilage regeneration; osteogenic abilities; endochondral ossification
Affiliations: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Department of Clinical Hematology, Third Military Medical University, Chongqing, China.

Abstract:  Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering. 

Retracted: No

PubPeer comments:
 Figure 2C. * Orange boxes: The Sox9 and GFP panels appear to show a large overlap. Reported to the journal in October 2015, but not addressed as of today. ![file] , 
 April 2021 Expression of Concern: https: journals.plos.org plosone article?id=10.1371 journal.pone.0249684  Following the publication of this article [1], concerns were raised regarding panels presented in Figs 1, 2 and 5. Specifically, * In the left panel of Fig 1C, the left side of the bands do not appear to align correctly with the right sides of the bands. * The Day 5 anti-u03b2-actin panel of Fig 1Db appears similar to the Day 5 u03b2-actin panel of Fig 5B. * The Sox9 panel and the GFP panel of Fig 2C partially overlap. * The Day 2 u03b2-actin panel of Fig 5B appears similar to the Day 14 u03b2-actin panel of Fig 5C when flipped.  The corresponding author has provided the original images underlying Fig 1C and indicated that black white inversion was performed to improve the presentation of the results. The uncropped underlying figures provided in the S1 File below support the panel presented in Fig 1C suggesting the irregularities in this figure are compression artifacts. The uncropped underlying blots and individual level data to support the published results presented in Fig 1D are summarised in the S2 and S3 Files below. The similarity between the Sox9 and GFP panel in Fig 2C is the result of an inadvertent error during figure assembly, whereby the wrong panel was used to represent the GFP results. The corresponding author provided an updated Fig 2 presenting the correct GFP panel. The individual data supporting the results presented in the updated Fig 2 are summarised in the S4 File below. The similarity between the western blot panels in Fig 1D and Fig 5B are the result of inadvertent errors during figure assembly. The corresponding author has indicated that the panels used to represent the Fig 5Ba Day 5 u03b2-actin results and the Fig 5Bc Day 14 u03b2-actin results are incorrect and proved an updated Fig 5 presenting the correct panels. In addition, the corresponding author indicated that the Fig 5Ba Day 5 Runx2 panel was presented upside-down. The underlying images and individual level data supporting the results presented in the updated Fig 5 are summarised in the supporting information S5u2013S8 Files. The PLOS ONE Editors issue this Expression of Concern to notify readers of the above concerns and relay the supporting data and updated figures provided by the corresponding author. ,