Impact of the host response and osteoblast lineage cells on periodontal disease

Abstract

Periodontitis involves the loss of connective tissue attachment and alveolar bone. Single cell RNA-seq experiments have provided new insight into how resident cells and infiltrating immune cells function in response to bacterial challenge in periodontal tissues. Periodontal disease is induced by a combined innate and adaptive immune response to bacterial dysbiosis that is initiated by resident cells including epithelial cells and fibroblasts, which recruit immune cells. Chemokines and cytokines stimulate recruitment of osteoclast precursors and osteoclastogenesis in response to TNF, IL-1β, IL-6, IL-17, RANKL and other factors. Inflammation also suppresses coupled bone formation to limit repair of osteolytic lesions. Bone lining cells, osteocytes and periodontal ligament cells play a key role in both processes. The periodontal ligament contains cells that exhibit similarities to tendon cells, osteoblast-lineage cells and mesenchymal stem cells. Bone lining cells consisting of mesenchymal stem cells, osteoprogenitors and osteoblasts are influenced by osteocytes and stimulate formation of osteoclast precursors through MCSF and RANKL, which directly induce osteoclastogenesis. Following bone resorption, factors are released from resorbed bone matrix and by osteoclasts and osteal macrophages that recruit osteoblast precursors to the resorbed bone surface. Osteoblast differentiation and coupled bone formation are regulated by multiple signaling pathways including Wnt, Notch, FGF, IGF-1, BMP, and Hedgehog pathways. Diabetes, cigarette smoking and aging enhance the pathologic processes to increase bone resorption and inhibit coupled bone formation to accelerate bone loss. Other bone pathologies such as rheumatoid arthritis, post-menopausal osteoporosis and bone unloading/disuse also affect osteoblast lineage cells and participate in formation of osteolytic lesions by promoting bone resorption and inhibiting coupled bone formation. Thus, periodontitis involves the activation of an inflammatory response that involves a large number of cells to stimulate bone resorption and limit osseous repair processes.

O‐GlcNAcylation of TLR4 inhibits osteogenic differentiation of periodontal ligament stem cells

“…PDLCs play a crucial role in the generation of periodontal ligament tissues, which may contribute to periodontitis therapy 19 . In addition, periodontitis involves an imbalance in bone resorption and bone formation, and diabetes can exacerbate this imbalance to accelerate inflammatory bone loss 20 . Therefore, promoting osteogenic differentiation and inhibiting osteoclastic absorption of PDLCs may contribute to decelerating the progression of diabetic periodontitis.…”

USP7 Inhibition Promotes Early Osseointegration in Senile Osteoporotic mice

“…First, it can promote the differentiation of monocyte lineage into osteoclasts, leading to bone resorption ( 37 ). Second, it can directly inhibit BMSCs osteogenic differentiation and osteoblast function, reducing bone formation ( 38 ). Third, it can further enhance the inflammatory response by promoting other immune cells such as neutrophils and T cells, etc ( 39 ).…”

Hispanic adults with type 2 diabetes mellitus using lipid-lowering agents have better periodontal health than non-users

“…The mechanism of action is dependent on a host-mediated tissue injury caused by the immune response that plays an important role in chronic periodontal tissue destruction. 1,2…”

“…The mechanism of action is dependent on a host-mediated tissue injury caused by the immune response that plays an important role in chronic periodontal tissue destruction. 1,2 PD is a major cause of tooth loss, which can compromise mastication, esthetics, self-confidence, and quality of life. 3 The prevalence of PD is approximately 42% in dentate Americans aged 30-79 years 4 and is even greater among the Hispanic population.…”