Osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8+ T cells

Abstract

Host immune response is known to contribute to the progression of periodontitis, and alveolar bone destruction in periodontitis is associated with enhanced osteoclast activity. Therefore, we evaluated the roles of activated lymphocyte subsets in osteoclastogenesis. Osteoclast precursors were co‐cultured with activated lymphocytes (B, CD4+ T, CD8+ T) in the presence of either macrophage colony‐stimulating factor (M‐CSF) alone or M‐CSF plus soluble receptor activator of NF‐κB ligand (sRANKL), and subsequent differentiation into active osteoclasts was evaluatedby a resorption assay. The activated B and CD4+ cells, but not CD8+ T cells, induced osteoclast differentiation in the presence of M‐CSF alone. In the presence of M‐CSF and sRANKL, B cells induced the formation of small but highly active osteoclasts and increased resorption, while CD8+ T cells profoundly suppressed osteoclastogenesis. Co‐culture using an insert wellor supernatant suggested that both B and CD8+ T cells acted on osteoclasts mostly via soluble proteins. Activated B cells expressed many osteoclastogenic factors including RANKL, TNF‐α, IL‐6, MIP‐1α, and MCP‐3. CD8+ T cells expressed a substantial amount of osteoprotegerin (OPG) along with RANKL. However, blocking antibody to OPG did not reverse the suppression by CD8+ T cells, suggesting that other factor(s) are involved. Taken together, activated B cells promoted osteoclastogenesis, while CD8+ T cells inhibited the osteoclast formation via direct interaction. The results imply the importance of lymphocyte subpopulations in the development of periodontitis.

OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis

“…For example, vitamin D3 stimulation of osteoclasts in vitro is enhanced by T-cell depletion (30); removing T cells would also remove any OX40 expressed by them. CD8 + T cells are also antiosteoclastogenic (15,31) and express high levels of OX40 during infections (32-34) associated with arthritic disease flare (35).…”

“…In the steady state, members of the TNF/TNF receptor superfamily play pivotal roles in multiple processes from lymphoid architecture to T-cell survival and bone homeostasis. RANK-L is a TNF family member produced by activated T cells (10,11), osteoblasts (12,13), keratinocytes (14), and B lymphocytes (15,16), among other cell types (reviewed in ref. 17), and, with macrophage colony-stimulating factor (M-CSF), drives osteoclast commitment from bone marrow precursors (18,19), leading to bone resorption.…”

Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss

“…In vitro studies have demonstrated that B cells at several stages of differentiation, from early precursors to plasma cells, can support osteoclast formation (16,(35)(36)(37)(38)(39). Nonetheless, Weitzmann and colleagues have shown that ovariectomy led to similar amounts of bone loss in mice lacking mature B cells compared with control littermates, suggesting that mature B cells are not required for the bone loss caused by estrogen deficiency (40).…”

Is periodontal disease mediated by salivary baff in sjögren's syndrome?

“…Likewise, the presence of advanced periodontal lesions has been ascribed to an infiltration of B lymphocytes in the gingiva of patients with periodontitis. These activated B cells induce osteoclast differentiation (5).…”