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

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.

Interaction between immuno-stem dual lineages in jaw bone formation and injury repair

“…In periodontal inflammation states, B cells produce higher TGF-β1 levels, inhibiting osteoblast activity ( CHEN et al, 2023 ). Switched memory B cells produce more RANKL ( HAN et al, 2018 ), leading eventually to alveolar bone loss.…”

A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy

“…4. TGF-β1 induces periodontal ligament stem cell senescence by increasing ROS production [ 60 – 63 ] IL-22 M2 Inhibits apoptosis of gingival epithelial cells during periodontitis [ 64 ] …”