Hematology Unit, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Int J Mol Sci. 2024 Jan 27;25(3):1598. doi: 10.3390/ijms25031598.
Osteonecrosis of the jaw is the progressive loss and destruction of bone affecting the maxilla or mandible in patients treated with antiresorptive and antiangiogenic agents without receiving prior radiation therapy. The pathogenesis involves the inflammatory pathway of receptor activator of nuclear factor NF-kB ligand and the macrophage colony-stimulating factor, essential for osteoclast precursors survival and proliferation and acting through its receptor c-Fms. Evidence has shown the role of non-coding RNAs in the pathogenesis of osteonecrosis of the jaw and this finding might be useful in diagnosis since these small RNAs could be considered as biomarkers of apoptotic activity in bone. Interestingly, it has been proved that miR-29 and miR-31-5p, acting on specific targets such as CALCR and RhoA, promote programmed-cell death and consequently the necrosis of bone tissue. Specific long non-coding RNAs, instead, have been detected both at reduced levels in patients with multiple myeloma and osteonecrosis, and associated with suppression of osteoblast differentiation, with consequences in the progression of mandible lesions. Among non-coding genic material, circular RNAs have the capability to modify the expression of specific mRNAs responsible for the inhibition of bisphosphonates activity on osteoclastogenesis.
颌骨骨坏死是一种进行性的骨丧失和破坏,影响接受抗吸收和抗血管生成药物治疗但未接受过放射治疗的患者的上颌骨或下颌骨。发病机制涉及核因子 NF-κB 配体受体激活剂和巨噬细胞集落刺激因子的炎症途径,这些对破骨细胞前体的存活和增殖至关重要,并通过其受体 c-Fms 发挥作用。有证据表明非编码 RNA 在颌骨骨坏死的发病机制中的作用,这一发现可能有助于诊断,因为这些小 RNA 可以被认为是骨细胞凋亡活性的生物标志物。有趣的是,已经证明 miR-29 和 miR-31-5p 通过作用于特定靶标如 CALCR 和 RhoA,促进程序性细胞死亡,从而导致骨组织坏死。相反,在多发性骨髓瘤和颌骨骨坏死患者中检测到特定的长非编码 RNA 水平降低,并与成骨细胞分化的抑制相关,从而导致下颌骨病变的进展。在非编码基因物质中,环状 RNA 能够修饰特定 mRNAs 的表达,这些 mRNAs负责抑制破骨细胞生成中双膦酸盐的活性。