Sclerostin regulation: a promising therapy for periodontitis by modulating alveolar bone

Abstract

Periodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.

The Impact of Dental Implant Surface Modifications on Osseointegration and Biofilm Formation

“…Sclerostin is an inhibitor of the Wnt/β-catenin signaling pathway that regulates bone growth [ 186 ]. It has become a therapeutic target for treating osteoporosis and is currently under study in dental implantology for its role in osseointegration [ 187 ]. Interestingly, expression of sclerostin and RANKL expression increased after an implant endures impact, suggesting sclerostin may be involved in the processes of peri-implant bone damage [ 188 ].…”

Gingival Mesenchymal Stem Cells Metabolite Decreasing TRAP, NFATc1, and Sclerostin Expression in LPS-Associated Inflammatory Osteolysis In Vivo

“…Sclerostin expression reduction would lead to increased bone formation by promoting the canonical Wnt-β catenin pathway and bone morphogenetic protein-2 gene. 30 31 Previous study found that sclerostin inhibition through utilization of antibodies altered its binding to LRP5/6, resulting in promoted bone regeneration. 30 Sclerostin was also reported to enhance RANKL expression in the Murine Osteocyte-like cell line (MLO-Y4), which is upregulated by TNF-α expression.…”

“… 30 31 Previous study found that sclerostin inhibition through utilization of antibodies altered its binding to LRP5/6, resulting in promoted bone regeneration. 30 Sclerostin was also reported to enhance RANKL expression in the Murine Osteocyte-like cell line (MLO-Y4), which is upregulated by TNF-α expression. 32 Utilization of TNF-α antagonists are reported to successfully ameliorate bone regeneration through downregulated sclerostin and RANKL expression, indicating that proinflammatory activities are necessary factors to the process.…”

Vitamin D Deficiency, Chronic Kidney Disease and Periodontitis

“…This concept was reinforced in an animal study where mice with chronic uraemia and hyperparathyroidism showed a significantly reduced cortical alveolar bone compared to healthy controls, and that a further decrease in bone levels was seen after a high phosphate diet was given to increase PTH hormone serum levels [ 109 ]. Furthermore, studies suggest that elevated levels of sclerostin in CKD increase the progression of periodontitis by inhibiting bone remodelling [ 110 , 111 , 112 ] and therefore, elevated sclerostin levels secondary to CKD-MBD may potentiate periodontitis-related alveolar bone loss [ 112 , 113 ].…”