B-Cell–Derived TGF-β1 Inhibits Osteogenesis and Contributes to Bone Loss in Periodontitis

B cells play a vital role in the elimination of periodontal pathogens, the regulation of the immune response, and the induction of tissue destruction. However, the role of B cells in the dysfunction of mesenchymal stem cell (MSC) differentiation to osteoblasts in periodontitis (PD) has been poorly s...

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Bibliographic Details
Published in:Journal of dental research 2023-07, Vol.102 (7), p.767-776
Main Authors: Chen, Y., Wang, H., Ni, Q., Wang, T., Bao, C., Geng, Y., Lu, Y., Cao, Y., Li, Y., Li, L., Xu, Y., Sun, W.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Alveolar bone
Alveolar Bone Loss
Animals
Ataxin
Bone loss
Cbfa-1 protein
CD105 antigen
CD19 antigen
CD27 antigen
CD38 antigen
CD45 antigen
CD73 antigen
Cell Differentiation
Gum disease
Immunological memory
Inflammation
Lymphocytes B
Memory cells
Mesenchymal stem cells
Mice
Osteoblastogenesis
Osteoblasts
Osteoblasts - metabolism
Osteoclasts - metabolism
Osteogenesis
Periodontitis
Smad2 protein
Transforming Growth Factor beta1 - metabolism
Transforming growth factor-b1
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Summary:B cells play a vital role in the elimination of periodontal pathogens, the regulation of the immune response, and the induction of tissue destruction. However, the role of B cells in the dysfunction of mesenchymal stem cell (MSC) differentiation to osteoblasts in periodontitis (PD) has been poorly studied. Here we show that the frequency of CD45−CD105+CD73+ MSCs in inflamed periodontal tissues is significantly decreased in patients with PD compared with that of healthy controls. CD19+ B cells dominate the infiltrated immune cells in periodontal tissues of patients with PD. Besides, B-cell depletion therapy reduces the alveolar bone loss in a ligature-induced murine PD model. B cells from PD mice express a high level of TGF-β1 and inhibit osteoblast differentiation by upregulating p-Smad2/3 expression and downregulating Runx2 expression. The inhibitory effect of PD B cells on osteoblast differentiation is reduced by TGF-β1 neutralization or Smad2/3 inhibitor. Importantly, B-cell–specific knockout of TGF-β1 in PD mice significantly increases the number of CD45−CD105+Sca1+ MSCs, ALP-positive osteoblast activity, and alveolar bone volume but decreases TRAP-positive osteoclast activity compared with that from control littermates. Lastly, CD19+CD27+CD38− memory B cells dominate the B-cell infiltrates in periodontal tissues from both patients with PD and patients with PD after initial periodontal therapy. Memory B cells in periodontal tissues of patients with PD express a high level of TGF-β1 and inhibit MSC differentiation to osteoblasts. Thus, TGF-β1 produced by B cells may contribute to alveolar bone loss in periodontitis, in part, by suppressing osteoblast activity.
ISSN:0022-0345
1544-0591
DOI:10.1177/00220345231161005