Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury...Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.展开更多
基金supported by the Key Program of the National Natural Science Foundation of China(32230059)the Basic Science Center Program(T2288102)+3 种基金the Foundation of Frontiers Sciesnce Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the National Natural Science Foundation of China(32401128)the Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251)。
文摘Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.
