Hepatocyte growth factor and insulin-like growth factor-1 were used to repair bone-cartilage defects in bone marrow mesenchymal stem cells in a rabbit model of postmenopausal

  • Jia-Qi Guan School of Clinical Medical, Shandong Second Medical University, Weifang 261053, China; National Tissue Engineering Center of China, Shanghai 261053, China
  • Chuan-Bo Zang School of Anesthesiology, Shandong Second Medical University, Weifang 216053, China
  • Jun-Cen Li School of Clinical Medical, Shandong Second Medical University, Weifang 261053, China; National Tissue Engineering Center of China, Shanghai 261053, China
  • Fei-Fan Chen National Tissue Engineering Center of China, Shanghai 261053, China
  • Ya-Hui Wang National Tissue Engineering Center of China, Shanghai 261053, China
  • Guang-Dong Zhou School of Clinical Medical, Shandong Second Medical University, Weifang 261053, China; National Tissue Engineering Center of China, Shanghai 261053, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Stem Cell Institute, Shanghai 2000336, China
  • Yu Liu School of Clinical Medical, Shandong Second Medical University, Weifang 261053, China; National Tissue Engineering Center of China, Shanghai 261053, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Stem Cell Institute, Shanghai 2000336, China
  • Yi-Lin Cao School of Clinical Medical, Shandong Second Medical University, Weifang 261053, China; National Tissue Engineering Center of China, Shanghai 261053, China; Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Stem Cell Institute, Shanghai 2000336, China
Keywords: postmenopausal osteoporosis; bone marrow mesenchymal stem cells; transcriptome sequencing; osteochondral defect; tissue engineering

Abstract

In postmenopausal osteoporosis (PMOP), an imbalance exists in the differentiation of bone marrow mesenchymal stem cells (BMSCs), with a decrease in osteogenic differentiation and an increase in adipogenic differentiation. This imbalance leads to bone marrow adiposity, bone loss, bone fragility, and a substantial rise in fracture risk. After a patient experiences an osteochondral defect due to trauma, it struggles to heal naturally, presenting a clinical challenge for treatment. Our study delved into the abnormal differentiation of BMSCs in PMOP by conducting transcriptome sequencing on BMSCs from a PMOP model (PMOP-BMSCs) and a healthy control model (Normal-BMSCs). We identified insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) genesas significantly low-expressed protein-coding genes during the osteogenic cartilage differentiation process of PMOP-BMSCs. Due to the downregulation of its expression, it leads to the deletion of the proteins it encodes IGF-1 and HGF. In order to verify the sequencing results, the feasibility of co-culture the above two growth factors with PMOP-BMSCs to repair osteochondral defects was discussed. The findings indicated that the inclusion of elements enhanced the DNA replication activity and extracellular matrix mineralization of PMOP-BMSCs. It also promoted the construction of tissue-engineered bone in vitro and the up- regulation of Runx2, BMP4, OCN, ACAN, collagen type Ⅰ, II, and Sox9 osteochondral differentiation markers. In the rabbit model of knee osteochondral injury with PMOP, the group treated with both growth factors and PMOP-BMSCs showed superior outcomes in repairing cartilage and subchondral bone defects compared to the other groups. We suggest that the addition of HGF and IGF-1 increases the expression of osteoblast and cartilage-related genes and proteins, promoting the proliferation and differentiation of osteochondrous bone in PMOP-BMSCs. These findings could offer a novel cell therapy strategy for treating postmenopausal osteoporosis, utilizing growth factors.

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Published
2024-06-17
How to Cite
Guan, J.-Q., Zang, C.-B., Li, J.-C., Chen, F.-F., Wang, Y.-H., Zhou, G.-D., Liu, Y., & Cao, Y.-L. (2024). Hepatocyte growth factor and insulin-like growth factor-1 were used to repair bone-cartilage defects in bone marrow mesenchymal stem cells in a rabbit model of postmenopausal. Molecular & Cellular Biomechanics, 21, 72. https://doi.org/10.62617/mcb.v21.72
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