Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been consid...Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.展开更多
Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlyi...Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlying this association remain unclear.This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions.Hypoxia upregulated methyltransferase-like protein 4(METTL4)expression in platelets,resulting in N6-methyladenine modification of mitochondrial DNA(mtDNA).This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation,leading to cytosolic mtDNA accumulation.Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets.This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis.Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology.Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.展开更多
Pathological mineralization,which encompasses conditions such as calculus,atherosclerotic calcified plaques,and heterotopic ossification in cartilage,leads to severe complications and has emerged as a significant medi...Pathological mineralization,which encompasses conditions such as calculus,atherosclerotic calcified plaques,and heterotopic ossification in cartilage,leads to severe complications and has emerged as a significant medical issue[1].Calculus refers to stones or calculi that form within the body,typically in organs such as the kidneys,bladder,or gallbladder[2].The cost of managing kidney stones is expected to increase to$1.24 billion per year by 2030[3].Since these strategies aim at removing the already formed stones rather than addressing the root causes,the recurrence and retreatment rate of kidney stones is quite high.The most common type of kidney stones,namely calcium oxalate kidney stones,are essentially the ectopic mineralization in the urinary system[4].However,the exact mechanisms that cause this form of ectopic mineralization are not fully understood.Hence,investigating the process of ectopic mineralization in kidney stone formation is a worthy and important endeavor.展开更多
基金National Nature Science Foundation of China 82471000(to K.J.)National Nature Science Foundation of China 82170978(to K.J.)+1 种基金National Nature Science Foundation of China 82325012(to L.N.N.)National Key Research and Development Program 2023YFC2509100(to K.J.)。
文摘Temporomandibular joint osteoarthritis(TMJ-OA)is a common disease often accompanied by pain,seriously affecting physical and mental health of patients.Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia,while the specific mechanism mediating pain remains unclear.To investigate the underlying mechanism of TMJ-OA pain,an abnormal joint loading model was used to induce TMJ-OA pain.We found that during the development of TMJ-OA,the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves.Furthermore,these two types of nerves are spatially closely associated.Additionally,it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice,whereas blocking these signals effectively alleviates pain.In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons.Moreover,we also discovered that through releasing norepinephrine,regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators.This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA.It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves,providing a potential target for treating TMJ-OA pain.
基金supported by the National Natural Science Foundation of China(82325012)the Youth Fund of the National Natural Science Foundation of China(82301043)+1 种基金the Natural Science Basic Research Program of Shaanxi (Program No.2024JC-YBQN-0980)the Shaanxi Key Scientific and Technological Innovation Team(2020TD-033).
文摘Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlying this association remain unclear.This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions.Hypoxia upregulated methyltransferase-like protein 4(METTL4)expression in platelets,resulting in N6-methyladenine modification of mitochondrial DNA(mtDNA).This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation,leading to cytosolic mtDNA accumulation.Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets.This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis.Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology.Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
基金National Natural Science Foundation of China(82325012)Shaanxi Key Scientific and Technological Innovation Team(2020TD-033).
文摘Pathological mineralization,which encompasses conditions such as calculus,atherosclerotic calcified plaques,and heterotopic ossification in cartilage,leads to severe complications and has emerged as a significant medical issue[1].Calculus refers to stones or calculi that form within the body,typically in organs such as the kidneys,bladder,or gallbladder[2].The cost of managing kidney stones is expected to increase to$1.24 billion per year by 2030[3].Since these strategies aim at removing the already formed stones rather than addressing the root causes,the recurrence and retreatment rate of kidney stones is quite high.The most common type of kidney stones,namely calcium oxalate kidney stones,are essentially the ectopic mineralization in the urinary system[4].However,the exact mechanisms that cause this form of ectopic mineralization are not fully understood.Hence,investigating the process of ectopic mineralization in kidney stone formation is a worthy and important endeavor.
