Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,t...DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,the functions of these duplicates in the teleost Nile tilapia(Oreochromis niloticus)remain unclear.In this study,we characterized the roles of Nile tilapia Sox9a in chondrogenesis and gonadal development.In situ hybridization assays showed that Sox9a was mainly expressed in cartilage tissues and somatic cells surrounding germ cells of the gonads.CRISPR/Cas9-mediated homozygous mutation of the Sox9a gene resulted in craniofacial deformities and missed mandibles,as well as impaired the expression of Col2a1a that is involved in chondrogenesis.In addition,germ cell number and DNA replication in somatic cells in the gonads of both sexes were reduced following Sox9a mutation.Taken together,this study demonstrates that Sox9a is involved in cartilage development and germ cell proliferation in Nile tilapia.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.
基金supported by the National Key Research and Development Program of China(2022YFD1201600)National Natural Science Foundation of China(31861123001,31302170,and 31772831)+1 种基金Chongqing Science and Technology Bureau(CSTB2022NSCQ-MSX1608 and cstc2021ycjh-bgzxm0024)Chongqing Fishery Technology Innovation Union(2023)。
文摘DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,the functions of these duplicates in the teleost Nile tilapia(Oreochromis niloticus)remain unclear.In this study,we characterized the roles of Nile tilapia Sox9a in chondrogenesis and gonadal development.In situ hybridization assays showed that Sox9a was mainly expressed in cartilage tissues and somatic cells surrounding germ cells of the gonads.CRISPR/Cas9-mediated homozygous mutation of the Sox9a gene resulted in craniofacial deformities and missed mandibles,as well as impaired the expression of Col2a1a that is involved in chondrogenesis.In addition,germ cell number and DNA replication in somatic cells in the gonads of both sexes were reduced following Sox9a mutation.Taken together,this study demonstrates that Sox9a is involved in cartilage development and germ cell proliferation in Nile tilapia.
