1. Academic Validation
  2. Poly-3-hydroxybutyrate-co-3-hydroxyvalerate(PHBV)-Polyethylene glycol 20k(PEG20k) as a promising delivery system for PT2399 in the treatment of disc degeneration

Poly-3-hydroxybutyrate-co-3-hydroxyvalerate(PHBV)-Polyethylene glycol 20k(PEG20k) as a promising delivery system for PT2399 in the treatment of disc degeneration

  • J Biol Eng. 2024 Jan 22;18(1):11. doi: 10.1186/s13036-024-00407-6.
Zhencong Li # 1 Weilin Zhang # 1 Shengbang Huang # 1 Zhiwen Dai 1 Jinguo Liang 1 Qiulan Qiu 2 Siyuan Chen 1 Weixiong Guo 1 Zhongwei Wang 1 Jinsong Wei 3
Affiliations

Affiliations

  • 1 Department of Spinal Degeneration and Deformity Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
  • 2 School of Public Health, Guangdong Medical University, Dongguan, 523808, China.
  • 3 Department of Spinal Degeneration and Deformity Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. jinsong.wei@gdmu.edu.cn.
  • # Contributed equally.
Abstract

Disc degeneration often leads to a highly prevalent symptom known as low back pain. Healthy nucleus pulposus tissue exhibited a hypoxic environment devoid of blood vessels, while degenerated nucleus pulposus experienced hypoxic deterioration and the formation of new blood vessels. In this study, the expression of important genes like HIF-2α was found to vary between normal and degenerated nucleus pulposus cells when compared to the hypoxic surroundings. The aim of this study was to examine how HIF-2α is controlled in nucleus pulposus cells under hypoxic conditions and its role in angiogenic mechanisms. To assess the impact of gradual inhibition of HIF-2α on disc degeneration, we utilized PHBV-based synthetic Materials loaded with inhibitors of HIF-2α. Specifically, we employed LPS and PT2399 loaded PHBV-PEG20k (PP20) to intervene with human nucleus pulposus cells. Additionally, we treated APD rat models with PT2399 loaded PP20 to evaluate its effects. The expression levels of target markers in nucleus pulposus cells were detected using PCR, WB, and immunofluorescence. Additionally, the effect of drugs on disc degeneration was identified through HE staining. The findings indicated that HIF-2α, CAIX, PPP1R15A, VEGFA, and EGLN3 could potentially serve as new Indicators of disc degeneration. Additionally, HIF-2α might contribute to the progression of disc degeneration through involvement in angiogenesis and the regulation of hypoxia. Furthermore, the utilization of PT2399 loaded PHBV-PEG20k (PP20) could potentially offer a fresh alternative for treating disc degeneration.

Keywords

Anoxic environment; HIF-2α; Nucleus pulposus; PHBV; PT2399.

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