RESUMEN
Osteoclasts are crucial in the events leading to bone metastasis of lung cancer. Interleukin-17A (IL-17A) affects osteogenesis by regulating the survival of osteoclast precursors (OCPs) and is enriched in lung cancer cells. However, how factors derived from tumor cells that metastasize to bone affect osteoclastogenesis remains poorly understood. We examined whether IL-17A derived from lung cancer cells affects osteoclast differentiation by regulating OCP apoptosis. IL-17A expression was inhibited in A549 non-small cell lung cancer cells using RNA interference. Compared with conditioned medium (CM) from A549 cells (A549-CM), CM from IL-17A-deficient A549 cells (A549-si-CM) suppressed osteoclastogenesis. The mRNA expression of osteoclast-specific genes was downregulated following A549-si-CM treatment. Furthermore, A549-si-CM promoted osteoclast precursor apoptosis at an early stage of osteoclastogenesis, which was related to the promotion of caspase-3 expression by A549-si-CM during osteoclast differentiation. In vivo experiments also showed that inhibition of IL-17A expression in A549 cells reduced osteoclast activation and bone tissue destruction. Collectively, our results indicate that IL-17A deficiency inhibits lung cancer-induced osteoclast differentiation by promoting apoptosis of osteoclast precursors in the early stage of osteoclast formation and that IL-17A is a potential therapeutic target for cancer-associated bone resorption in patients with lung cancer.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Diferenciación Celular/fisiología , Interleucina-17/genética , Interleucina-17/metabolismo , Neoplasias Pulmonares/patología , Osteoclastos/metabolismo , Osteogénesis/genética , Ligando RANK/metabolismoRESUMEN
Biochar is an emerging eco-friendly and high-efficiency heavy metal (HM) adsorbent that exhibits satisfactory HM remediation effects in both water and soil environments. However, few studies have investigated the mechanisms and application of biochar in the remediation of combined HM-contaminated environments. Therefore, in the present study, a novel corn straw biochar-loaded calcium-iron layered double hydroxide composite (CaFe-LDH@CSB) was synthesized via the coprecipitation method and applied as a remediation adsorbent to remove HMs in both water and soil environments. The results indicated that the HM adsorption mechanism of CaFe-LDH@CSB in the aquatic phase involved a chemical endothermic adsorption process of functional group-complexed monolayers, dominated by precipitation, ion exchange, complexation and π bond interactions. The maximum adsorption capacity for Cd(II), Pb(II), Zn(II) and Cu(II) in the aqueous phase reached 24.58, 240.96, 57.57 and 39.35 mg g-1, respectively. In addition, application of CaFe-LDH@CSB in the combined HM-contaminated soil treatment helped to increase the soil pH, which increased by 5.1-17.9% in low-contamination (LC) soil and by 7.0-13.9% in high-contamination (HC) soil. Moreover, application of CaFe-LDH@CSB effectively decreased the acid-soluble fraction of HMs and increased the HM residual fraction. The immobilization mechanism of CaFe-LDH@CSB in the soil was concluded to involve pore filling, functional group action and electrostatic interactions. Overall, this study provided a novel LDH biochar composite that can be effectively applied in the remediation of combined HM-contaminated water and soil environments.