ABSTRACT
Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Subject(s)
Animals , Mice , Interleukin-10 , Bifidobacterium breve , Up-Regulation , Angiogenesis Inhibitors , Sunitinib , X-Ray Microtomography , Administration, Oral , Wound Healing , Antibodies, NeutralizingABSTRACT
Objective:To understand the clinical features of osteonecrosis of the jaw after bisphospho-nates use for therapy of breast cancer patients with bone metastasis.Methods:The cases diagnosed as bisphosphonates-related osteonecrosis of the jaws (BRONJ)were retrospectively analyzed from January 201 1 to August 201 5 in the Peking University School and Hospital of Stomatology,and those breast cancer patients with bone metastasis were selected.The clinical symptoms,imaging characteristics and treatment results were summarized.Results:A total of 1 4 cases of breast cancer patients with bone me-tastasis were selected,with an average age of 60.21 years.The average time of suffering from breast cancer was 9 .77 years,and the average time of bone metastasis and bisphosphonates drugs use was 5 .67 and 3 .29 years individually.There was no patient with systemic application history of hormone therapy, and no history of diabetes.There were 9 patients with tooth extractions history,and the mean time of bone necrosis symptoms was 8.58 months.There were 1 0 cases with bone necrosis occurring on mandi-ble,3 cases on maxilla,and one case with both upper and lower jaws involved.Among the 1 0 patients with surgical treatment,there were 3 cases cured,and 6 cases improved.However,the clinical symp-toms of 2 cases with conservative treatment were significantly aggravated.Conclusion:The medication time between the bisphosphonates use beginning and the occurrence of BRONJ is relatively long.The his-tory of diabetes and long-time hormone use did not exist in this group.Tooth extraction itself does not de-termine the severity of BRONJ.Mandible is the most common site involved by BRONJ.Surgical treatment can alleviate the clinical symptoms of BRONJ with breast cancer to some extent.
ABSTRACT
<p><b>OBJECTIVE</b>To retrospectively analyze the data of the patients with Bisphosphonate-related osteonecrosis of the jaw over the past five years in our hospital.</p><p><b>METHODS</b>Twenty-four patients with bisphosphonate-related osteonecrosis of the jaw treated in our hospital from 2009 to 2013 were included. The medication, bisphosphonate types, clinical signs and symptom, treatment methods and results were also analyzed.</p><p><b>RESULTS</b>Of the 24 cases, 20 cases suffered from malignant tumors and received intravenous infusion of bisphosphonates and 4 cases took oral bisphosphonates. Three of the 4 cases with osteoporosis had history of glucocorticoid (rheumatoid arthritis). All patients had oral clinical symptoms for an average of 11.6 months, and 19 patients had the history of tooth extraction. There were 11 cases with mandible involved, 10 cases with maxilla involved, and 3 cases with both mandible and maxilla involved. After conservative treatment (3 cases) or operation (21 cases), 10 cases had wound healing, 6 cases were stable with bone exposure, and 4 cases with died bone needed reoperation. During the follow-up period, there was one patient died of primary disease (renal carcinoma).</p><p><b>CONCLUSIONS</b>Both intravenous and oral application routes of bisphosphonates can induce osteonecrosis of the jaw. Bisphosphonate-related osteonecrosis of the jaw can be caused by alveolar trauma. The treatment modality is to relieve the clinical symptoms of bisphosphonate-related osteonecrosis of the jaw.</p>