Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (31): 8060-8067.doi: 10.12307/2026.435

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Molecular mechanism of polygonatum sibiricum polysaccharide-promoted chondrogenic differentiation of adipose-derived stem cells

Chen Junjie1, He Jiayang2, Wang Zihe1, Peng Teng3, Liu Yingqi4, 5, Li Sen6, Li Jingchi7, Wang Guoyou1, 8, Li Ting9, Yu Wanxin10, Shen Huarui1, 8   

  1. 1Department of Joint Surgery, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Southwest Medical University, Luzhou 646000, Sichuan Province, China; 3School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China; 4School of Materials and Energy, Southwest University, Chongqing 400715, China; 5Affiliated Hospital of Southwest University, Chongqing 400700, China; 6Department of Orthopedics, Gulou Hospital Affiliated to Nanjing University Medical School, Nanjing 210003, Jiangsu Province, China; 7Department of Spinal Surgery, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 8Department of Orthopedics, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Key Laboratory of Orthopedic Diseases, Luzhou 646000, Sichuan Province, China; 9School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 10School of Biomedical Engineering & Med-X Institute, Shanghai Jiao Tong University, Shanghai 200030, China
  • Received:2025-10-17 Accepted:2026-01-29 Online:2026-11-08 Published:2026-05-22
  • Contact: Shen Huarui, MS, Chief physician, Department of Joint Surgery, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Orthopedics, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Key Laboratory of Orthopedic Diseases, Luzhou 646000, Sichuan Province, China
  • About author:Chen Junjie, MD candidate, Physician, Department of Joint Surgery, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Sichuan Provincial Science and Technology Plan, No. 2024NSFSC0570 (to SHR); Southwest Medical University Project, No. 2023ZYYJ05 (to SHR); Sichuan Provincial Administration of Traditional Chinese Medicine Project, No. 2024zd018 (to SHR); Luzhou Municipal Government-Southwest Medical University Science and Technology Strategic Cooperation Project, No. 2021LZXNYD-J31 (to SHR); 2022 Research Team Cultivation Project of Southwest Medical University Affiliated Traditional Chinese Medicine Hospital, No. 2022-CXTD-08 (to SHR); Chongqing Municipal Natural Science Foundation (General Program), No. CSTB2023NSCQ-MSX0644 (to LYQ); Chongqing Municipal Key Construction Discipline of Traditional Chinese Medicine-Southwest University Traditional Chinese Medicine Rehabilitation, No. 2021-4322190044 (to LYQ)

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Abstract: BACKGROUND: Polygonatum sibiricum polysaccharide is the main active component of the traditional Chinese medicine polygonatum and has anti-inflammatory, antioxidant, and tissue repair properties. Recent studies have shown that polygonatum sibiricum polysaccharide may play an important role in bone and cartilage metabolism. 
OBJECTIVE: To investigate the effect and mechanism of polygonatum sibiricum polysaccharide combined with transforming growth factor-β3 on inducing the differentiation of rat adipose-derived stem cells into chondrocytes.
METHODS: Adipose-derived stem cells were isolated from rat inguinal fat using enzymatic digestion. First, the effect of different mass concentrations of polygonatum sibiricum polysaccharide on adipose-derived stem cell proliferation was detected using the CCK-8 assay to screen for the optimal proliferative concentration. Then, adipose-derived stem cells were divided into four groups for chondrogenic differentiation induction: control group, polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group. Cell morphology observation, toluidine blue staining, immunofluorescence staining, and western blot assay were used to detect the expression of chondrogenic differentiation markers. Western blot assay was used to detect the expression of related proteins in the transforming growth factor β3/Smad2 signaling pathway. To verify whether polygonatum sibiricum polysaccharide and transforming growth factor β3 regulate chondrogenic differentiation through the transforming growth factor β3/Smad2 pathway, the transforming growth factor β3 receptor kinase inhibitor SB-505124 was used to specifically block the pathway. Adipose-derived stem cells were divided into five groups: control group, inhibitor group, polygonatum sibiricum polysaccharide + inhibitor group, transforming growth factor β3 + inhibitor group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 + inhibitor group. Western blot assay was used to detect the expression of cartilage differentiation markers and proteins related to the transforming growth factor β3/Smad2 signaling pathway. 
RESULTS AND CONCLUSION: (1) The CCK-8 assay determined that 5 mg/L of polygonatum sibiricum polysaccharide was the optimal intervention concentration. (2) Toluidine blue staining showed that the blue-stained area in the polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group was significantly higher than that in the control group (P < 0.05). (3) Immunofluorescence staining further confirmed that compared with the control group, the fluorescence intensity of type II collagen α1 chain was significantly enhanced in the polygonatum sibiricum polysaccharide group and the polygonatum sibiricum polysaccharide + transforming growth factor β3 group, with the highest fluorescence intensity in the polygonatum sibiricum polysaccharide + transforming growth factor β3 group (P < 0.05). (4) Western blot assay showed that compared with the control group, the polygonatum sibiricum polysaccharide group, transforming growth factor β3 group, and polygonatum sibiricum polysaccharide + transforming growth factor β3 group significantly upregulated the p-Smad2/Smad2 and the protein expression levels of cartilage markers type II collagen α1 chain, Sox9, and aggrecan (P < 0.05), and the combined treatment group showed the highest protein expression levels of these indicators (P < 0.05). (5) After adding the transforming growth factor β receptor kinase inhibitor, compared with the inhibitor group, the protein expression levels of the above indicators were significantly increased in the other groups (P < 0.05). The results indicate that polygonatum sibiricum polysaccharide induces the differentiation of adipose-derived stem cells into chondrocytes by activating the transforming growth factor β/Smad2 signaling pathway.

Key words: cartilage injury, polygonatum sibiricum polysaccharide, transforming growth factor β3/Smad signaling pathway, adipose-derived stem cells, chondrogenic induction, osteoarthritis, transforming growth factor-β3, cell differentiation

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