
Journal of Shanghai Jiao Tong University (Medical Science) >
Effect of jaw osteoblasts on B cell development via cytokine secretion
Received date: 2025-02-19
Accepted date: 2025-04-29
Online published: 2025-09-30
Supported by
“Two-Hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20221809);National Natural Science Foundation of China(82430032);National Key Research and Development Program of China(2024YFC2510700);Shanghai Science and Technology Innovation Action Plan International Science and Technology Cooperation Program(23410713600);Natural Science Foundation of Shanghai(21ZR1436900);Cross-Disciplinary Research Fund of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine(JYJC202116);Biomaterials and Regenerative Medicine Institute Cooperative Research Project, Shanghai Jiao Tong University School of Medicine(2022LHB02)
Objective ·To investigate the regulatory effects and underlying mechanisms of mouse mandibular osteoblasts on B cell differentiation and development. Methods ·Single-cell suspensions from mouse mandibular bone were prepared using an optimized enzymatic digestion method and induced to differentiate into osteoblasts in vitro. Osteogenic potential was validated by real-time quantitative PCR (RT-qPCR), alkaline phosphatase (ALP) staining, and alizarin red S (ARS) staining. The spatial localization relationship between osteoblasts and B cells in mandibular tissues was examined via immunofluorescence staining. High-purity hematopoietic progenitor cells were isolated using fluorescence-activated cell sorting. A Transwell co-culture system was established to assess the regulatory effects of different osteoblast concentrations (5×104, 2.5×105, and 5×105 cells/well) on B cell differentiation (5×104 cells/well). Flow cytometry and RT-qPCR were employed to evaluate B cell viability and differentiation. Additionally, RT-qPCR was used to analyze the expression of osteoblast-secreted factors associated with B cell development during osteogenic differentiation. Results ·Mandibular osteoblasts exhibited robust osteogenic potential, as confirmed by ALP/ARS staining and high expression of osteogenic markers (Runx2, Osx, Ocn, and Alp) via RT-qPCR. Immunofluorescence revealed close spatial proximity between osteoblasts and B cells in mandibular tissues. In the co-culture system, osteoblasts promoted B cell differentiation in a concentration-dependent manner. RT-qPCR and immunofluorescence demonstrated that osteoblasts significantly upregulated key genes involved in B cell development (Ebf1, Rag1, Il7r, and Pax5; all P<0.001). Furthermore, osteoblast-derived factors (Il7, Baff, and Flt3l) were markedly elevated during osteogenic differentiation (all P<0.05). Conclusion ·Mandibular osteoblasts enhance B cell differentiation and development in a concentration-dependent manner, likely through secreting growth factors that upregulate critical B cell differentiation genes.
Key words: jaw osteoblasts; osteoimmunology; B lymphocytes; immunoregulation
WANG Xinyu , CHEN Qianye , SUN Jiping , LU Tingwei , HUANG Xiangru , SUN Siyuan , LIU Yuanqi , PAN Houwen , DAI Qinggang , SHEN Lei , JIANG Lingyong . Effect of jaw osteoblasts on B cell development via cytokine secretion[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(9) : 1106 -1115 . DOI: 10.3969/j.issn.1674-8115.2025.09.003
| [1] | XU H, LI Y, GAO Y. The role of immune cells settled in the bone marrow on adult hematopoietic stem cells[J]. Cell Mol Life Sci, 2024, 81(1): 420. |
| [2] | DE HAAN G,LAZARE S S. Aging of hematopoietic stem cells[J]. Blood, 2018, 131(5): 479-487. |
| [3] | ROSS J B, MYERS L M, NOH J J, et al. Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity[J]. Nature, 2024, 628(8006): 162-170. |
| [4] | NAKAMURA-ISHIZU A, ITO K, SUDA T. Hematopoietic stem cell metabolism during development and aging[J]. Dev Cell, 2020, 54(2): 239-255. |
| [5] | KOH B I, MOHANAKRISHNAN V, JEONG H W, et al. Adult skull bone marrow is an expanding and resilient haematopoietic reservoir[J]. Nature, 2024, 636(8041): 172-181. |
| [6] | AGHALOO T L, CHAICHANASAKUL T, BEZOUGLAIA O, et al. Osteogenic potential of mandibular vs. long-bone marrow stromal cells[J]. J Dent Res, 2010, 89(11): 1293-1298. |
| [7] | SELLERI L, RIJLI F M. Shaping faces: genetic and epigenetic control of craniofacial morphogenesis[J]. Nat Rev Genet, 2023, 24(9): 610-626. |
| [8] | YANG Y L, DAI Q G, GAO X, et al. Occlusal force orchestrates alveolar bone homeostasis via Piezo1 in female mice[J]. J Bone Miner Res, 2024, 39(5): 580-594. |
| [9] | SVANDOVA E, PETERKOVA R, MATALOVA E, et al. Formation and developmental specification of the odontogenic and osteogenic mesenchymes[J]. Front Cell Dev Biol, 2020, 8: 640. |
| [10] | LAM N, LEE Y, FARBER D L. A guide to adaptive immune memory[J]. Nat Rev Immunol, 2024, 24(11): 810-829. |
| [11] | ZHONG X, MORESCO J J, KELLER K, et al. Essential requirement for IER3IP1 in B cell development[J]. Proc Natl Acad Sci USA, 2023, 120(46): e2312810120. |
| [12] | DOORES K J. Humoral immunity to phlebovirus infection[J]. Ann N Y Acad Sci, 2023, 1530(1): 23-31. |
| [13] | KLOC M, HALASA M, KUBIAK J Z, et al. Invertebrate immunity, natural transplantation immunity, somatic and germ cell parasitism, and transposon defense[J]. Int J Mol Sci, 2024, 25(2): 1072. |
| [14] | CEKICI A, KANTARCI A, HASTURK H, et al. Inflammatory and immune pathways in the pathogenesis of periodontal disease[J]. Periodontol 2000, 2014, 64(1): 57-80. |
| [15] | ZOU J, ZENG Z J, XIE W, et al. Immunotherapy with regulatory T and B cells in periodontitis[J]. Int Immunopharmacol, 2022, 109: 108797. |
| [16] | ZHANG M, LIU Y, AFZALI H, et al. An update on periodontal inflammation and bone loss[J]. Front Immunol, 2024, 15: 1385436. |
| [17] | SHI T, JIN Y, MIAO Y B, et al. IL-10 secreting B cells regulate periodontal immune response during periodontitis[J]. Odontology, 2020, 108(3): 350-357. |
| [18] | LIU Z, LUO X, XU R. Interaction between immuno-stem dual lineages in jaw bone formation and injury repair[J]. Front Cell Dev Biol, 2024, 12: 1359295. |
| [19] | NEURATH N, KESTING M. Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets[J]. Front Immunol, 2024, 15: 1435054. |
| [20] | PAJARINEN J, LIN T, GIBON E, et al. Mesenchymal stem cell-macrophage crosstalk and bone healing[J]. Biomaterials, 2019, 196: 80-89. |
| [21] | GARG V, GIRADDI G B, ROY S. Comparison of efficacy of mandible and iliac bone as autogenous bone graft for orbital floor reconstruction[J]. J Maxillofac Oral Surg, 2015, 14(2): 291-298. |
| [22] | MERTENS C, DECKER C, SEEBERGER R, et al. Early bone resorption after vertical bone augmentation: a comparison of calvarial and iliac grafts[J]. Clin Oral Implants Res, 2013, 24(7): 820-825. |
| [23] | SCHLUNDT C, FISCHER H, BUCHER C H, et al. The multifaceted roles of macrophages in bone regeneration: a story of polarization, activation and time[J]. Acta Biomater, 2021, 133: 46-57. |
| [24] | LUO W, DU C Y, HUANG H, et al. The role of macrophage death in periodontitis: a review[J]. Inflammation, 2024, 47(6): 1889-1901. |
| [25] | RASTOGI I, JEON D, MOSEMAN J E, et al. Role of B cells as antigen presenting cells[J]. Front Immunol, 2022, 13: 954936. |
| [26] | MAURI C. Regulation of immunity and autoimmunity by B cells[J]. Curr Opin Immunol, 2010, 22(6): 761-767. |
| [27] | ZHANG H, WANG R, WANG G, et al. Single-cell RNA sequencing reveals B cells are important regulators in fracture healing[J]. Front Endocrinol (Lausanne), 2021, 12: 666140. |
| [28] | FISCHER V, HAFFNER-LUNTZER M. Interaction between bone and immune cells: implications for postmenopausal osteoporosis[J]. Semin Cell Dev Biol, 2022, 123: 14-21. |
| [29] | LIU L, CHEN Y, WANG L, et al. Dissecting B/plasma cells in periodontitis at single-cell/bulk resolution[J]. J Dent Res, 2022, 101(11): 1388-1397. |
| [30] | ZHOU M, GRAVES D T. Impact of the host response and osteoblast lineage cells on periodontal disease[J]. Front Immunol, 2022, 13: 998244. |
| [31] | PIETSCHMANN P, BUTYLINA M, KERSCHAN-SCHINDL K, et al. Mechanisms of systemic osteoporosis in rheumatoid arthritis[J]. Int J Mol Sci, 2022, 23(15): 8740. |
| [32] | ZHOU R, GUO Q, XIAO Y, et al. Endocrine role of bone in the regulation of energy metabolism[J]. Bone Res, 2021, 9(1): 25. |
| [33] | WU M, WU S, CHEN W, et al. The roles and regulatory mechanisms of TGF?β and BMP signaling in bone and cartilage development, homeostasis and disease[J]. Cell Res, 2024, 34(2): 101-123. |
| [34] | LI L, LIU Y J, QIAN X S, et al. Modulating the phenotype and function of bone marrow-derived macrophages via mandible and femur osteoblasts[J]. Int Immunopharmacol, 2024, 132: 112000. |
| [35] | XIONG Y, MI B B, LIN Z, et al. The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity[J]. Mil Med Res, 2022, 9(1): 65. |
| [36] | CAI B, LIN D, LI Y, et al. N2-polarized neutrophils guide bone mesenchymal stem cell recruitment and initiate bone regeneration: a missing piece of the bone regeneration puzzle[J]. Adv Sci (Weinh), 2021, 8(19): e2100584. |
| [37] | YAMASHIRO K, IDEGUCHI H, AOYAGI H, et al. High mobility group box 1 expression in oral inflammation and regeneration[J]. Front Immunol, 2020, 11: 1461. |
| [38] | WINTER J, JEPSEN S. Role of innate host defense proteins in oral cancerogenesis[J]. Periodontol 2000, 2024, 96(1): 203-220. |
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