Key Takeaways & Executive Findings
- •• Xuling Jiangu Formula significantly increased bone mineral density in ovariectomized osteoporotic rats. • The formula modulated the Treg/Th17 balance by increasing Treg numbers and decreasing Th17-related cytokine secretion. • It upregulated forkhead box P3 and downregulated retinoic acid-related orphan receptor γt, altering the OPG/RANKL ratio. • The immunomodulatory effects of Xuling Jiangu Formula contribute to its anti-osteoporotic activity.
Abstract
BACKGROUND: Osteoporosis is not only a metabolic disease, but also an inflammatory or autoimmune disease. Immune cells Treg and Th17 have a mutually antagonistic effect on the differentiation and maturation of osteoclasts, and the maintenance of cell balance between the two is the basis for ensuring normal bone metabolism. OBJECTIVE: To explore the immunomodulatory mechanism of Xuling Jiangu Formula on osteoporosis and its relationship with the balance of Treg/Th17 cells. METHODS: Sprague-Dawley rats were randomly divided into a sham operation group, a model group, and a drug group, with eight rats in each group. The latter two groups underwent bilateral ovariectomy to establish the animal model; the sham operation group underwent the same procedure except for ovary removal. Four weeks after modeling, bone mineral density was measured using dual-energy X-ray absorptiometry to evaluate whether the modeling was successful. Drug intervention started 4 weeks after surgery: the Xuling Jiangu Formula group was given 10 mL/kg Xuling Jiangu Formula by gavage once daily for 16 weeks; the model and sham operation groups were given the same volume of normal saline. After 16 weeks of drug administration, bone mineral density and blood routine parameters were measured, bone tissue morphology was observed by hematoxylin-eosin staining, serum immune factor levels were detected by ELISA, and the gene and protein expressions of osteoprotegerin, receptor activator of nuclear factor-κB ligand, retinoic acid-related orphan receptor γt, and forkhead box P3 were detected by quantitative PCR and western blot. The numbers of Treg and Th17 cells were detected by flow cytometry. RESULTS AND CONCLUSION: After 16 weeks of administration, compared with the model group, the bone mineral density of rats in the Xuling Jiangu Formula group was significantly increased (P < 0.05), serum levels of interleukin-10 and transforming growth factor-β were increased but without significant difference, while levels of interleukin-17 and interleukin-6 were significantly decreased (P < 0.05). After 16 weeks of administration, the gene and protein expressions of osteoprotegerin and Treg marker gene forkhead box P3 were significantly increased (P < 0.05), while the gene and protein expressions of Th17 marker gene retinoic acid-related orphan receptor γt were significantly decreased (P < 0.05), and the protein expression of receptor activator of nuclear factor-κB ligand was significantly decreased (P < 0.05), but the gene expression showed a decreasing trend without significant difference. Flow cytometry results showed that the number of Treg cells was significantly increased (P < 0.05), while the number of Th17 cells was decreased but not statistically significant. These findings suggest that the immune mechanism of Xuling Jiangu Formula in treating osteoporosis is to affect the Treg/Th17 balance by increasing the number of Treg cells, then reduce the secretion of interleukin-17 and interleukin-6, promote the upregulation of forkhead box P3 and downregulation of retinoic acid-related orphan receptor γt, thereby changing the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio, and subsequently inhibit osteoclast differentiation.
1. Introduction
Osteoporosis is a metabolic bone disease, and its incidence continues to rise with the aging population [1]. Regulatory T cells (Tregs) and Th17 cells, as immune cells, participate in multiple biological processes. Studies have shown that the ratio of Tregs to Th17 cells is closely related to bone metabolism [2-3]. Our previous research found that Xuling Jiangu Formula has good clinical efficacy in treating osteoporosis [4], and its mechanism is related to the Treg-specific transcription factor forkhead box P3 (Foxp3) [5]. Therefore, we conducted an in vivo study on osteoporosis model rats, using flow cytometry and molecular biology to verify the immune mechanism of Xuling Jiangu Formula in intervening osteoporosis model rats, providing experimental evidence for the treatment of osteoporosis with this compound.
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Huang Jingwen, Li Shengqiang, Jiang Hong, Chen Xuan, Ye Yunjin, Ge Jirong (2026). Immunological mechanisms of Xuling Jiangu Formula in intervening osteoporosis model rats. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21487
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Frequently Asked Questions
What is Xuling Jiangu Formula?
Xuling Jiangu Formula is an empirical anti-osteoporosis prescription developed by the research group based on long-term clinical practice. It has significant therapeutic effects on postmenopausal osteoporosis in clinical treatment and animal experiments. The formula has the effects of tonifying the kidney and strengthening bones, invigorating the spleen and replenishing qi, and promoting blood circulation to relieve pain.
How does Xuling Jiangu Formula affect the immune system in osteoporosis?
The formula modulates the immune system by increasing the number of regulatory T cells (Tregs), which affects the Treg/Th17 balance. This leads to decreased secretion of interleukin-17 and interleukin-6, upregulation of forkhead box P3, downregulation of retinoic acid-related orphan receptor γt, and alteration of the OPG/RANKL ratio, ultimately inhibiting osteoclast differentiation.
What was the experimental design of this study?
In this study, 24 female Sprague-Dawley rats were randomly divided into sham operation, model, and drug groups. The model and drug groups underwent bilateral ovariectomy to induce osteoporosis. After 4 weeks, the drug group received Xuling Jiangu Formula (10 mL/kg) daily for 16 weeks, while the other groups received saline. Various parameters including bone mineral density, serum cytokines, gene/protein expression, and Treg/Th17 cell numbers were measured.
What were the key findings of the study?
The study found that Xuling Jiangu Formula significantly increased bone mineral density, increased Treg numbers, decreased Th17-related cytokines (IL-17, IL-6), upregulated Foxp3, downregulated RORγt, and altered the OPG/RANKL ratio, suggesting a mechanism involving Treg/Th17 balance modulation.
What are the clinical implications of this research?
This research provides experimental evidence supporting the use of Xuling Jiangu Formula as an immunomodulatory therapy for osteoporosis, potentially offering a novel approach to treatment by targeting the immune-bone interaction.
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