Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast...Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.展开更多
Bone mesenchymal stem cells(BMSCs)are stem cells located in the bone marrow matrix that have a variety of differentiation potentials and biological functions.They play an important role in bone regenerative medicine.T...Bone mesenchymal stem cells(BMSCs)are stem cells located in the bone marrow matrix that have a variety of differentiation potentials and biological functions.They play an important role in bone regenerative medicine.The senescence of BMsCs might cause accelerated degeneration of bone tissue.Autophagy is a process in which cellular homeostasis is maintained by autophagosomes and lysosomes.It could control the function and senescence of BMSCs during bone aging and might be a therapeutic target for treating diseases during aging.1 Ferroptosis is a regulated cell death process.2 The inhibition of ferroptosis in mesenchymal stem cells could reduce cell injury and might have great therapeutic value.3-5.展开更多
To the Editor: Parkinson's disease (PD) is a common degenerative disease of the central nervous systern (CNS) in middle-aged and elderly people. PD is characterized by resting tremor, myotonia, bradykinesia, abn...To the Editor: Parkinson's disease (PD) is a common degenerative disease of the central nervous systern (CNS) in middle-aged and elderly people. PD is characterized by resting tremor, myotonia, bradykinesia, abnormal posture, and gait. The incident of PD increases with age. In addition to motor symptoms, nonmotor symptoms have raised additional concerns in recent years. Cognitive impairment is very common in PD patients. It is estimated that the incidence of PD mild cognitive impairment (PD-MCI) is 20 50%, which is present at the initial visit in some patients and a great number of patients with PD-MCI eventually develop PD with dementia (PDD).展开更多
基金supported by the National Natural Science Foundation of China(Nos.82272157,82072425,and 82072498)the Natural Science Foundation of Jiangsu Province(No.BE2021650)+3 种基金the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,the Program of Suzhou Health Commission(Nos.GSWS2022002 and GSWS2020121)the Jiangsu Medical Research Project(No.ZD2022014)the National and Local Engineering Laboratory of New Functional Polymer Materials(No.SDGC2205)the Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(No.LCZX202003),China.
文摘Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.
基金supported by the National Natural Science Foundation of China(No.82072425)the Natural Science Foundation of Jiangsu Province,China(No.BK20220059)the Jiangsu Medical Research Project(China)(No.ZD2022021)。
文摘Bone mesenchymal stem cells(BMSCs)are stem cells located in the bone marrow matrix that have a variety of differentiation potentials and biological functions.They play an important role in bone regenerative medicine.The senescence of BMsCs might cause accelerated degeneration of bone tissue.Autophagy is a process in which cellular homeostasis is maintained by autophagosomes and lysosomes.It could control the function and senescence of BMSCs during bone aging and might be a therapeutic target for treating diseases during aging.1 Ferroptosis is a regulated cell death process.2 The inhibition of ferroptosis in mesenchymal stem cells could reduce cell injury and might have great therapeutic value.3-5.
文摘To the Editor: Parkinson's disease (PD) is a common degenerative disease of the central nervous systern (CNS) in middle-aged and elderly people. PD is characterized by resting tremor, myotonia, bradykinesia, abnormal posture, and gait. The incident of PD increases with age. In addition to motor symptoms, nonmotor symptoms have raised additional concerns in recent years. Cognitive impairment is very common in PD patients. It is estimated that the incidence of PD mild cognitive impairment (PD-MCI) is 20 50%, which is present at the initial visit in some patients and a great number of patients with PD-MCI eventually develop PD with dementia (PDD).