Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway

Yang,Junlong; Wang,Liu; Zhang,Zhongjie; Sun,Qing; Zhang,Yuan

doi:10.3892/ijmm.2023.5260

Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway

Authors:
- Junlong Yang
- Liu Wang
- Zhongjie Zhang
- Qing Sun
- Yuan Zhang
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Affiliations: Department of Pain, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Department of Pain, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637002, P.R. China, Department of Pain, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Department of Orthopedic Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: May 25, 2023 https://doi.org/10.3892/ijmm.2023.5260
Article Number: 57
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a progressive joint disorder, which is principally characterized by the degeneration and destruction of articular cartilage. The cytoskeleton is a vital structure that maintains the morphology and function of chondrocytes, and its destruction is a crucial risk factor leading to chondrocyte degeneration and OA. Hyaluronan synthase‑2 (HAS‑2) is a key enzyme in synthesizing hyaluronic acid (HA) in vivo. The synthesis of high molecular weight HA catalyzed by HAS‑2 serves a vital role in joint movement and homeostasis; however, it is unclear what important role HAS‑2 plays in maintaining chondrocyte cytoskeleton morphology and in cartilage degeneration. The present study downregulated the expression of HAS‑2 by employing 4‑methylumbelliferone (4‑MU) and RNA interference. In vitro experiments, including reverse transcription‑quantitative PCR, western blotting, laser scanning confocal microscopy and flow cytometry were subsequently performed. The results revealed that downregulation of HAS‑2 could activate the RhoA/ROCK signaling pathway, cause morphological abnormalities, decrease expression of the chondrocyte cytoskeleton proteins and promote chondrocyte apoptosis. In vivo experiments, including immunohistochemistry and Mankin's scoring, were performed to verify the effect of HAS‑2 on the chondrocyte cytoskeleton, and it was revealed that inhibition of HAS‑2 could cause cartilage degeneration. In conclusion, the present results revealed that downregulation of HAS‑2 could activate the RhoA/ROCK pathway, cause abnormal morphology and decrease chondrocyte cytoskeleton protein expression, leading to changes in the signal transduction and biomechanical properties of chondrocytes, promotion of chondrocyte apoptosis and the induction of cartilage degeneration. Moreover, the clinical application of 4‑MU may cause cartilage degeneration. Therefore, targeting HAS‑2 may provide a novel therapeutic strategy for delaying chondrocyte degeneration, and the early prevention and treatment of OA.

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