BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchyma...BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchymal stem cells(MSCs)derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors.The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.AIM To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis(AS-MSCs)inhibit osteoclastogenesis.METHODS We analysed fat mass and obesity-associated(FTO)protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase,nuclear factor of activated T cells 1 and cathepsin K.RESULTS We found that FTO,an enzyme responsible for removing methyl groups from RNA,was more abundantly expressed in MSCs from AS patients than in those from healthy donors.Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development.Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage(NORAD)by altering its N6-methyladenosine methylation status.Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284,which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.CONCLUSION This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.展开更多
Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO...Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.展开更多
Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain...Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain,joint stiffness,and loss of joint function,and OA has the higher prevalence rate and has been listed as one of the four major disabling diseases,seriously affecting people’s lives and health.Traditional Chinese medicine(TCM)is a comprehensive science based on the theory of Yin Yang(one TCM theory,the material world is believed to be nurtured,developed,and changed under the influence of Yin and Yang)and Five Elements(The five most basic substances-wood,fire,earth,metal,and water-are considered indispensable elements that make up the world),based on TCM theory and practical experience it can play the important role in prevention,diagnosis,treatment,rehabilitation,and health care in OA,exhibit the great application potential for OA treatment.In this review,we have summarized the recent research progress in the application of TCM in OA,including an analysis of underlying mechanisms,application limitations,and potential solutions,found that the material basis and targets of the therapeutic component of TCM,the quality control and the mechanism of TCM application in OA are not very clear,which may become the application limitation of TCM in OA.We hope that this review will offer valuable insights to researchers in the field.展开更多
基金Supported by Guangdong Provincial Clinical Research Center for Orthopedic Diseases,No.2023B110001the Excellent Medical Innovation Talent Program of the Eighth Affiliated Hospital of Sun Yat-sen University,No.YXYXCXRC202101+3 种基金the National Natural Science Foundation of China,No.82172349,No.82372372,No.22105229,No.32170708,No.82102530,No.82102541,No.82103098,No.82103909,No.82104182,No.82104350,No.82170427,No.82171291,No.82172215,No.82172385,and No.82302661Guangdong Natural Science Foundation,No.2023A1515010568 and No.2021A1515111057Shenzhen Science and Technology Program,No.JCYJ20220530144201004 and No.RCBS20210609104445097Futian Healthcare Research Project,No.FTWS2022022,No.FTWS2021013,No.FTWS2023072,and No.FTWS2022047.
文摘BACKGROUND Ankylosing spondylitis(AS)is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints,alongside abnormal bone growth.In previous studies,we reported that mesenchymal stem cells(MSCs)derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors.The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.AIM To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis(AS-MSCs)inhibit osteoclastogenesis.METHODS We analysed fat mass and obesity-associated(FTO)protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase,nuclear factor of activated T cells 1 and cathepsin K.RESULTS We found that FTO,an enzyme responsible for removing methyl groups from RNA,was more abundantly expressed in MSCs from AS patients than in those from healthy donors.Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development.Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage(NORAD)by altering its N6-methyladenosine methylation status.Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284,which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.CONCLUSION This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.
基金supported by the following funds:The National Natural Science Foundation of China(Nos.52275393,51935014,and 82072084)Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)+2 种基金The Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performancethe National Key Research and Development Program of China(No.2023YFB4605800)the Independent Exploration and Innovation Project of Central South University(No.1053320221707).
文摘Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.
文摘Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain,joint stiffness,and loss of joint function,and OA has the higher prevalence rate and has been listed as one of the four major disabling diseases,seriously affecting people’s lives and health.Traditional Chinese medicine(TCM)is a comprehensive science based on the theory of Yin Yang(one TCM theory,the material world is believed to be nurtured,developed,and changed under the influence of Yin and Yang)and Five Elements(The five most basic substances-wood,fire,earth,metal,and water-are considered indispensable elements that make up the world),based on TCM theory and practical experience it can play the important role in prevention,diagnosis,treatment,rehabilitation,and health care in OA,exhibit the great application potential for OA treatment.In this review,we have summarized the recent research progress in the application of TCM in OA,including an analysis of underlying mechanisms,application limitations,and potential solutions,found that the material basis and targets of the therapeutic component of TCM,the quality control and the mechanism of TCM application in OA are not very clear,which may become the application limitation of TCM in OA.We hope that this review will offer valuable insights to researchers in the field.
