SFMBT2 positively regulates SOX9 and chondrocyte proliferation

Hussain,Safdar; Sun,Mengyao; Guo,Yuanxu; Mushtaq,Nosheen; Zhao,Yitong; Yuan,Ying; Hussain,Nazim; Osoro,Ezra; Suleiman,Abubakar; Sadiq,Muhammad; Zhang,Fujun; Han,Yan; Sun,Jian; Lu,Shemin

doi:10.3892/ijmm.2018.3894

SFMBT2 positively regulates SOX9 and chondrocyte proliferation

Authors:
- Safdar Hussain
- Mengyao Sun
- Yuanxu Guo
- Nosheen Mushtaq
- Yitong Zhao
- Ying Yuan
- Nazim Hussain
- Ezra Osoro
- Abubakar Suleiman
- Muhammad Sadiq
- Fujun Zhang
- Yan Han
- Jian Sun
- Shemin Lu
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Department of Microbiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Centre for Applied Molecular Biology (CAMB), University of The Punjab, Lahore 53700, Pakistan
Published online on: September 25, 2018 https://doi.org/10.3892/ijmm.2018.3894
Pages: 3503-3512

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Abstract

SRY‑box 9 (SOX9) is the master regulator of the chondrocyte phenotype, which is essential for differentiating chondrogenic mesenchymal condensations into chondrocytes, and is involved in regulating every stage of chondrocyte differentiation. SOX9 deletion in chondrocytes at the late stages of cartilage development results in decreased chondrocyte proliferation; inhibited expression of cartilage matrix genes, including Indian hedgehog and the downstream parathyroid hormone‑related protein; and premature conversion of proliferating chondrocytes into hypertrophic chondrocytes, which mineralize their matrix prematurely. Therefore, SOX9 is considered vital for the majority of phases of chondrocyte lineage, from early condensations to the differentiation of proliferating chondrocytes, leading to chondrocyte hypertrophy. It has been reported that SOX9 expression is decreased in osteoarthritis (OA) cartilage. Regeneration or repair of cartilage degradation in OA remains a challenge. Previous studies have indicated that overexpression of SOX9 can promote cartilage repair and can be used as a potential therapeutic agent at the early stages of human OA. The present study identified Scm‑like with four malignant brain tumor domains 2 (SFMBT2) as a novel regulator of SOX9 expression in human chondrocytes. Our previous study revealed that SFMBT2 is negatively regulated in OA cartilage, and decreased levels of SFMBT2 contribute to the catabolic phenotype of chondrocytes. The present study detected increased expression levels of SFMBT2 in early cartilage development and during the early phases of chondrogenesis. Overexpression of SFMBT2 in C28/I2 cells upregulated SOX9 expression in a dose‑dependent manner. Furthermore, SFMBT2 positively regulated C28/I2 cell proliferation and restored the decreased levels of SOX9 in chondrocytes following tumor necrosis factor‑α treatment. Additional studies may reveal novel insights into the molecular mechanism involved and the potential role of SFMBT2 in cartilage repair and OA management.

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