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Article Open Access

UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy

  • Authors:
    • Qiqian Yan
    • Shanwei Shi
    • Yang Ge
    • Shuangquan Wan
    • Mingfei Li
    • Maoquan Li
  • View Affiliations / Copyright

    Affiliations: Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 99
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    Published online on: September 1, 2023
       https://doi.org/10.3892/ijmm.2023.5302
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Abstract

Stem cell‑based tissue engineering has shown significant potential for rapid restoration of injured cartilage tissues. Stem cells frequently undergo apoptosis because of the prevalence of oxidative stress and inflammation in the microenvironment at the sites of injury. Our previous study demonstrated that stabilization of hypoxia‑inducible factor 1α (HIF‑1α) is key to resisting apoptosis in chondrocytes. Recently, it was reported that Ubiquitin C‑terminal hydrolase L1 (UCHL1) can stabilize HIF‑1α by abrogating the ubiquitination process. However, the effect of UCHL1 on apoptosis in chondrocytes remains unclear. Herein, adipose‑derived stem cells were differentiated into chondrocytes. Next, the CRISPR activation (CRISPRa) system, LDN‑57444 (LDM; a specific inhibitor for UCHL1), KC7F2 (a specific inhibitor for HIF‑1α), and 3‑methyladenine (a specific inhibitor for mitophagy) were used to activate or block UCHL1, HIF‑1α, and mitophagy. Mitophagy, apoptosis, and mitochondrial function in chondrocytes were detected using immunofluorescence, TUNEL staining, and flow cytometry. Moreover, the oxygen consumption rate of chondrocytes was measured using the Seahorse XF 96 Extracellular Flux Analyzer. UCHL1 expression was increased in hypoxia, which in turn regulated mitophagy and apoptosis in the chondrocytes. Further studies revealed that UCHL1 mediated hypoxia‑regulated mitophagy in the chondrocytes. The CRISPRa module was utilized to activate UCHL1 effectively for 7 days; endogenous activation of UCHL1 accelerated mitophagy, inhibited apoptosis, and maintained mitochondrial function in the chondrocytes, which was mediated by HIF‑1α. Taken together, UCHL1 could block apoptosis in chondrocytes via upregulation of HIF‑1α-mediated mitophagy and maintain mitochondrial function. These results indicate the potential of UCHL1 activation using the CRISPRa system for the regeneration of cartilage tissue.
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Copy and paste a formatted citation
Spandidos Publications style
Yan Q, Shi S, Ge Y, Wan S, Li M and Li M: UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy. Int J Mol Med 52: 99, 2023.
APA
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., & Li, M. (2023). UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy. International Journal of Molecular Medicine, 52, 99. https://doi.org/10.3892/ijmm.2023.5302
MLA
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., Li, M."UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy". International Journal of Molecular Medicine 52.4 (2023): 99.
Chicago
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., Li, M."UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy". International Journal of Molecular Medicine 52, no. 4 (2023): 99. https://doi.org/10.3892/ijmm.2023.5302
Copy and paste a formatted citation
x
Spandidos Publications style
Yan Q, Shi S, Ge Y, Wan S, Li M and Li M: UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy. Int J Mol Med 52: 99, 2023.
APA
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., & Li, M. (2023). UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy. International Journal of Molecular Medicine, 52, 99. https://doi.org/10.3892/ijmm.2023.5302
MLA
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., Li, M."UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy". International Journal of Molecular Medicine 52.4 (2023): 99.
Chicago
Yan, Q., Shi, S., Ge, Y., Wan, S., Li, M., Li, M."UCHL1 alleviates apoptosis in chondrocytes via upregulation of HIF‑1α‑mediated mitophagy". International Journal of Molecular Medicine 52, no. 4 (2023): 99. https://doi.org/10.3892/ijmm.2023.5302
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