Role of dendritic cell‐mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw

Abstract

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood.Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue-resident DCs, promoting disruption of T-cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC-deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T-cell activation. We conclude that the mechanism of Zolinduced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response. K E Y W O R D S alveolar bone healing, dendritic cells, osteonecrosis 2596 | ELSAYED Et AL.

Porphyromonas gingivalis Provokes Exosome Secretion and Paracrine Immune Senescence in Bystander Dendritic Cells

“…Generation of BMDCs was performed as previously described ( Elashiry et al., 2020 ; Elsayed et al., 2020 ). Briefly, bone marrow was isolated from femurs and tibiae of young (2 months) and old (22-24 months) C57B6 mice.…”

Enterococcus faecalis Induces Differentiation of Immune-Aberrant Dendritic Cells from Murine Bone Marrow-Derived Stem Cells

“…Antigen presentation. To study the antigen-presenting ability of E. faecalis-induced DCs for CD4 ϩ T cells, the spleens of OT-II transgenic mice were dissected, and T cells were isolated to 95% purity using negative selection with a mouse T cell enrichment kit (MagniSort; Thermo fisher Scientific) and then stained with CFSE as previously described (47). The E. faecalis-induced DCs and control DCs were incubated with OVA peptide (O1641; MilliporeSigma).…”

The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw

“…Orsini et al demonstrated that BPs modulate the maturation of DCs but have no effect on the differentiation of DCs ( 42 ). Recently, it was shown that zoledronate (nitrogen-containing BPs) treatment decreased the number of infiltrated DCs in soft tissues and impaired the phagocytosis of DCs, thereby leading to an increased bacterial load and the occurrence of MRONJ ( 43 ). There are few reports on the underlying mechanism of BPs-mediated dysfunction of DCs, however, the immune suppression and inflammation in the oral cavity caused by dysfunctional DCs may provide new insights into the pathogenesis of MRONJ.…”

“…Additionally, decades of reports have identified that immune cells participate and mediate skeletal homeostasis by releasing multiple types of cytokines ( 94 ). Elsayed et al found that DCs play a significant role in post-extraction homeostasis in alveolar bone ( 43 ). Osteal macrophages were reported to locate adjacent to osteoblasts and regulate bone formation, playing diverse roles in skeletal homeostasis ( 95 ).…”