MicroRNA-130b downregulation potentiates chondrogenic differentiation of bone marrow mesenchymal stem cells by targeting SOX9.

Penggui Zhang,Xuejun He,Ziyu Zhou,Guangming Gao

doi:10.1590/1414-431x202010345

Penggui Zhang, Xuejun He + Show 2 more

Open Access

https://doi.org/10.1590/1414-431x202010345

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Abstract

Osteoarthritis (OA) is a chronic health condition. MicroRNAs (miRs) are critical in chondrocyte apoptosis in OA. We aimed to investigate the mechanism of miR-130b in OA progression. Bone marrow mesenchymal stem cells (BMSCs) and chondrocytes were first extracted. Chondrogenic differentiation of BMSCs was carried out and verified. Chondrocytes were stimulated with interleukin (IL)-1β to imitate OA condition in vitro. The effect of miR-130b on the viability, inflammation, apoptosis, and extracellular matrix of OA chondrocytes was studied. The target gene of miR-130b was predicted and verified. Rescue experiments were performed to further study the underlying downstream mechanism of miR-130b in OA. miR-130b first increased and drastically reduced during chondrogenic differentiation of BMSCs and in OA chondrocytes, respectively, while IL-1β stimulation resulted in increased miR-130b expression in chondrocytes. miR-130b inhibitor promoted chondrogenic differentiation of BMSCs and chondrocyte growth and inhibited the levels of inflammatory factors. miR-130b targeted SOX9. Overexpression of SOX9 facilitated BMSC chondrogenic differentiation and chondrocyte growth, while siRNA-SOX9 contributed to the opposite trends. Silencing of SOX9 significantly attenuated the pro-chondrogenic effects of miR-130b inhibitor on BMSCs. Overall, miR-130b inhibitor induced chondrogenic differentiation of BMSCs and chondrocyte growth by targeting SOX9.

Highlights

Osteoarthritis (OA), a prevalent, progressive, and degenerative joint disorder, is characterized by articular cartilage degeneration, joint impairment, and abnormalities in other joint tissues, such as the synovial membrane and ligaments [1,2]
The cells had typical spindle shape in spiral or clustered growth, which are the typical features of Bone marrow mesenchymal stem cells (BMSCs)
We verified in this study that miR-130b inhibitor potentiated chondrogenic differentiation of BMSCs and chondrocyte growth by targeting SRYbox transcription factor 9 (SOX9)

Summary

Introduction

Osteoarthritis (OA), a prevalent, progressive, and degenerative joint disorder, is characterized by articular cartilage degeneration, joint impairment, and abnormalities in other joint tissues, such as the synovial membrane and ligaments [1,2]. OA is a common chronic health condition, leading to severe pain and disability [3], affecting more than 151 million individuals globally [4]. OA is a key contributor to pain, stiffness, disability, poor quality of life, and limited activities of daily life [2]. OA is usually diagnosed via clinical and radiographic changes during the irreversible stages when the treatment of OA is largely palliative, only to slow the progression and reduce the pain [6]. The exploration of novel biological markers and more effective approaches could lay a theoretical foundation for OA treatment

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