Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (29): 6187-6197.doi: 10.12307/2025.772

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Therapeutic effect of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rat models: fecal metabolomics analysis

Chai Jinlian1, Sun Tiefeng2, Li Wei3, Zhang Bochun3, Li Guangzheng4, Zhou Zhongqi4, Liang Xuezhen3, 5, Wang Ping2   

  1. 1College of Pharmacy, 4College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 2Shandong Provincial Research Institute of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 3First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 5Department of Orthopedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • Received:2024-09-18 Accepted:2024-11-12 Online:2025-10-18 Published:2025-03-06
  • Contact: Liang Xuezhen, MD, Associate professor, Master’s supervisor, First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; Department of Orthopedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China Corresponding author: Wang Ping, PhD, Researcher, Master’s supervisor, Shandong Provincial Research Institute of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • About author:Chai Jinlian, MS, College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82205154 (to LXZ); Shandong Natural Science Foundation (Youth Project), No. ZR2021QH004, ZR2024MH156 (to LXZ); Shandong Natural Science Foundation, No. ZR2020MH386 (to WP)

Abstract: BACKGROUND: Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Colla can enter the bone, promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, and has a good repair effect on steroid-induced osteonecrosis of the femoral head.
OBJECTIVE: To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics. 
METHODS: Thirty SD rats were randomly divided into three groups using a random number table method: the control group (n=10) was injected with normal saline into the right gluteal muscle (injected on the first 3 days of each week for 3 consecutive weeks), and was given pure water gavage (once a day for 6 consecutive weeks). The model group (n=10) was injected with methylprednisolone sodium succinate into the right gluteal muscle (injected on the first 3 days of each week for 3 consecutive weeks) to establish a steroid-induced osteonecrosis of the femoral head model, and was given pure water gavage (once a day for 6 consecutive weeks). The Cornus Cervi Colla group (n=10) was also established with a steroid-induced osteonecrosis of the femoral head model, and was given Cornus Cervi Colla gavage (once a day for 6 consecutive weeks). After gavage, cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining, respectively.
RESULTS AND CONCLUSION: (1) Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Colla and model groups, with 65 significantly differing and clearly annotated metabolites. Lipid and amino acid metabolites were significantly increased, with bile acids, sulfated steroids, ephedrine, hypoxanthine, betaine, L-carnitine, B-mouse bile acid, cytidine, 4-pyridoxic acid, taurine, N-acetyl-d-glucosamine, and butyric acid being the most impacted (variable weight value VIP > 5). The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network (pathway impact=0.428 57). (2) Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Colla group had different degrees of damage; the femoral head contour was irregular; the trabeculae in the subchondral bone of the femoral head were missing and disordered, and some cystic structures were visible. Compared with the model group, the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder. Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted, and the empty bone lacuna rate and adipocyte invasion were increased. Compared with the model group, the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced. (3) These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Key words: Cornus Cervi Colla, steroid-induced osteonecrosis of the femoral head, metabolomics, bile acid metabolism, taurine, engineered tissue construction

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