2. Academic Validation
  3. Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells

Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells

  • Cell Death Dis. 2017 May 18;8(5):e2801. doi: 10.1038/cddis.2017.208.
Zhenhui Lu 1 2 3,  Danqing Lei 4,  Tongmeng Jiang 1 2 3 5,  Lihui Yang 6,  Li Zheng 1 2 3,  Jinmin Zhao 1 2 3 5
Affiliations

Affiliations

  • 1 Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 2 Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 3 Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 4 The Medical and Scientific Research Center, Guangxi Medical University, Nanning, China.
  • 5 Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 6 School of Nursing, Guangxi Medical University, Nanning, China.
PMID: 28518137 DOI: 10.1038/cddis.2017.208
Abstract

Growth factors such as transforming growth factor beta1 (TGF-β1), have critical roles in the regulation of the chondrogenic differentiation of mesenchymal stem cells (MSCs), which promote cartilage repair. However, the clinical applications of the traditional growth factors are limited by their high cost, functional heterogeneity and unpredictable effects, such as cyst formation. It may be advantageous for cartilage regeneration to identify a low-cost substitute with greater chondral specificity and easy accessibility. As a neuropeptide, nerve growth factor (NGF) was involved in cartilage metabolism and NGF is hypothesized to mediate the chondrogenic differentiation of MSCs. We isolated NGF from Chinese cobra venom using a three-step procedure that we had improved upon from previous studies, and investigated the chondrogenic potential of NGF on bone marrow MSCs (BMSCs) both in vitro and in vivo. The results showed that NGF greatly upregulated the expression of cartilage-specific markers. When applied to cartilage repair for 4, 8 and 12 weeks, NGF-treated BMSCs have greater therapeutic effect than untreated BMSCs. Although inferior to TGF-β1 regarding its chondrogenic potential, NGF showed considerably lower expression of Collagen type I, which is a fibrocartilage marker, and RUNX2, which is critical for terminal chondrocyte differentiation than TGF-β1, indicating its chondral specificity. Interestingly, NGF rarely induced BMSCs to differentiate into a neuronal phenotype, which may be due to the presence of Other chondrogenic supplements. Furthermore, the underlying mechanism revealed that NGF-mediated chondrogenesis may be associated with the activation of PI3K/Akt and MAPK/ERK signaling pathways via the specific receptor of NGF, TrkA. In addition, NGF is easily accessed because of the abundance and low price of cobra venom, as well as the simplified methods for separation and purification. This study was the first to demonstrate the chondrogenic potential of NGF, which may provide a reference for cartilage regeneration in the clinic.

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