B-Cell–Derived TGF-β1 Inhibits Osteogenesis and Contributes to Bone Loss in Periodontitis. (July 2023)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of dental research. Volume 102:Number 7(2023)
• Page Start: 767
• Page End: 776
• Publication Date: 2023-07
• Subjects: bone remodeling -- immunity -- mesenchymal stem cells -- osteoblasts -- osteoclasts -- periodontal diseases; Dentistry -- Periodicals; Dentistry -- Social aspects -- Periodicals; Dentistry -- Periodicals; Research -- Periodicals; 617.6005
• DOI: 10.1177/00220345231161005
• Languages: English
• ISSNs: 0022-0345

Abstract

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.