Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro
Rheumatoid arthritis (RA) is characterized by an impaired articular bone immune microenvironment, which is associated with regulatory T cells (Tregs) hypofunction and osteoclasts (OCs) hyperfunction and leads to articular bone erosion and systemic bone loss. Studies have shown that Tregs slow bone l...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.746786/full |
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| author | Ya Xia Danping Fan Danping Fan Danping Fan Xiaoya Li Xiangchen Lu Xiangchen Lu Xiangchen Lu Qinbin Ye Xiaoyu Xi Qiong Wang Hongyan Zhao Cheng Xiao Cheng Xiao Cheng Xiao |
| author_facet | Ya Xia Danping Fan Danping Fan Danping Fan Xiaoya Li Xiangchen Lu Xiangchen Lu Xiangchen Lu Qinbin Ye Xiaoyu Xi Qiong Wang Hongyan Zhao Cheng Xiao Cheng Xiao Cheng Xiao |
| author_sort | Ya Xia |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is characterized by an impaired articular bone immune microenvironment, which is associated with regulatory T cells (Tregs) hypofunction and osteoclasts (OCs) hyperfunction and leads to articular bone erosion and systemic bone loss. Studies have shown that Tregs slow bone loss in RA by regulating the bone resorption function of OCs and the JAK/STAT signaling pathway can regulate the immunosuppressive function of Tregs and reduce the bone erosion function of OCs. Yi Shen Juan Bi Pill (YSJB) is a classic Chinese herbal compound for the treatment of RA. However, whether YSJB regulates bone immune microenvironment homeostasis through JAK/STAT signaling pathway remains unclear. Based on in vitro OC single culture, Treg single culture and OC-Treg coculture systems, treatments were performed using drug-containing serum, AG490 and JAK2 siRNA to explore whether YSJB-containing serum regulates the homeostasis of the bone immune microenvironment through the JAK/STAT signaling pathway. In vitro, YSJB treatment decreased the number of TRAP+ cells and the areas of bone resorption and inhibited the expression of RANK, NFATc1, c-fos, JAK2, and STAT3 in both the OC single culture system and the OC-Treg coculture system. Tregs further reduced the number of TRAP+ cells and the areas of bone resorption in the coculture system. YSJB promoted the secretion of IL-10 while inhibiting the expression of JAK2 and STAT3 in Tregs. Moreover, inhibiting the expression of JAK2 with the JAK2 inhibitor AG490 and JAK2 siRNA improved the immunosuppressive functions of Treg, inhibited OC differentiation and bone resorption. Our study demonstrates that YSJB can regulate OC-mediated bone resorption and Treg-mediated bone immunity through the JAK2/STAT3 signaling pathway. This study provides a new strategy for regulating the bone immune microenvironment in RA with traditional Chinese medicine. |
| first_indexed | 2024-12-13T21:22:10Z |
| format | Article |
| id | doaj.art-4154045f330b42ff9c446688ab35e1e6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T21:22:10Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-4154045f330b42ff9c446688ab35e1e62022-12-21T23:31:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-12-011210.3389/fphar.2021.746786746786Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in VitroYa Xia0Danping Fan1Danping Fan2Danping Fan3Xiaoya Li4Xiangchen Lu5Xiangchen Lu6Xiangchen Lu7Qinbin Ye8Xiaoyu Xi9Qiong Wang10Hongyan Zhao11Cheng Xiao12Cheng Xiao13Cheng Xiao14School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Emergency, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaThe Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaPinggu Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Emergency, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, ChinaInstitute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, ChinaRheumatoid arthritis (RA) is characterized by an impaired articular bone immune microenvironment, which is associated with regulatory T cells (Tregs) hypofunction and osteoclasts (OCs) hyperfunction and leads to articular bone erosion and systemic bone loss. Studies have shown that Tregs slow bone loss in RA by regulating the bone resorption function of OCs and the JAK/STAT signaling pathway can regulate the immunosuppressive function of Tregs and reduce the bone erosion function of OCs. Yi Shen Juan Bi Pill (YSJB) is a classic Chinese herbal compound for the treatment of RA. However, whether YSJB regulates bone immune microenvironment homeostasis through JAK/STAT signaling pathway remains unclear. Based on in vitro OC single culture, Treg single culture and OC-Treg coculture systems, treatments were performed using drug-containing serum, AG490 and JAK2 siRNA to explore whether YSJB-containing serum regulates the homeostasis of the bone immune microenvironment through the JAK/STAT signaling pathway. In vitro, YSJB treatment decreased the number of TRAP+ cells and the areas of bone resorption and inhibited the expression of RANK, NFATc1, c-fos, JAK2, and STAT3 in both the OC single culture system and the OC-Treg coculture system. Tregs further reduced the number of TRAP+ cells and the areas of bone resorption in the coculture system. YSJB promoted the secretion of IL-10 while inhibiting the expression of JAK2 and STAT3 in Tregs. Moreover, inhibiting the expression of JAK2 with the JAK2 inhibitor AG490 and JAK2 siRNA improved the immunosuppressive functions of Treg, inhibited OC differentiation and bone resorption. Our study demonstrates that YSJB can regulate OC-mediated bone resorption and Treg-mediated bone immunity through the JAK2/STAT3 signaling pathway. This study provides a new strategy for regulating the bone immune microenvironment in RA with traditional Chinese medicine.https://www.frontiersin.org/articles/10.3389/fphar.2021.746786/fullrheumatoid arthritisYi Shen Juan Bi Pillosteoclastregulatory T cellJAK2/STAT3 signaling pathway |
| spellingShingle | Ya Xia Danping Fan Danping Fan Danping Fan Xiaoya Li Xiangchen Lu Xiangchen Lu Xiangchen Lu Qinbin Ye Xiaoyu Xi Qiong Wang Hongyan Zhao Cheng Xiao Cheng Xiao Cheng Xiao Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro Frontiers in Pharmacology rheumatoid arthritis Yi Shen Juan Bi Pill osteoclast regulatory T cell JAK2/STAT3 signaling pathway |
| title | Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro |
| title_full | Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro |
| title_fullStr | Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro |
| title_full_unstemmed | Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro |
| title_short | Yi Shen Juan Bi Pill Regulates the Bone Immune Microenvironment via the JAK2/STAT3 Signaling Pathway in Vitro |
| title_sort | yi shen juan bi pill regulates the bone immune microenvironment via the jak2 stat3 signaling pathway in vitro |
| topic | rheumatoid arthritis Yi Shen Juan Bi Pill osteoclast regulatory T cell JAK2/STAT3 signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.746786/full |
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