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| 1 | Cartilage repair techniques of the talus: An update显示文摘Symptomatic chondral or osteochondral defects of the talus reduce the quality of life of many patients.Although their pathomechanism is well understood,it is well known that different aetiologic factors play a role in their origin.Additionally,it is well recognised that the talar articular cartilage strongly differs from that in the knee.Despite this fact,many recommendations for the management of talar cartilage defects are based on approaches that were developed for the knee.Conservative treatment seems to work best in paediatric and adolescent patients with osteochondritis dissecans.However,depending on the size of the lesions,surgical approaches are necessary to treat many of these defects.Bone marrow stimulation techniques may achieve good results in small lesions.Large lesions may be treated by open procedures such as osteochondral autograft transfer or allograft transplantation.Autologous chondrocyte transplantation,as a restorative procedure,is well investigated in the knee and has been applied in the talus with increasing popularity and promising results but the evidence to date is poor.The goals of the current article are to summarise the different options for treating chondral and osteochondral defects of the talus and review the available literature. | Mike H Baums Wolfgang Schultz Tanja Kostuj Hans-Michael Klinger | 2014 | World Journal of Orthopedics2014，5，3： | 11 |
| 2 | Experimental Study on the Suppression of Sodium Nitroprussiate-lnduced Chondrocyte Apoptosis by Tougu Xiaotong Capsule(透骨消痛胶囊)-Containing Serum显示文摘Objective:To study the mechanism of action of Tougu Xiaotong Capsule(透骨消痛胶囊,TGXTC) ex vivo in suppressing chondrocyte(CD) apoptosis induced by sodium nitroprussiate(SNP).Methods:Thirty New Zealand rabbits,2 months old,were randomized by lottery into five groups,six in each:the blank group treated with saline,the positive control group treated with Zhuanggu Guanjie Pill(壮骨关节丸,70 mg/kg),and the three experimental groups,EGA,EGB,and EGC,treated with low dose(35 mg/kg),moderate dose(70 mg/kg),and high dose(140 mg/kg) of TGXTC,respectively.All treatments were administered via gastrogavage twice a day for 3 days.Arterial blood was collected from the abdominal aorta and drug or drug metabolites-containing serum was prepared.CDs obtained from knee joints of 16 four-week-old New Zealand rabbits were cultured to the third passage and confirmed by toluidine blue staining.SNP of various final concentrations(0,0.5,1.0,and 2.0 mmol/L) was used to induce CD apoptosis,and the dosage-effect relationship of SNP in inducing CD apoptosis was determined.Serum samples from the blank,control,and three dosages of TGXTC-treated rabbits were tested in the CD culture in the presence of SNP.Cell apoptosis was determined by Hoechst 33342 staining,viability of CDs was quantified by MTT,CD apoptosis rate was determined by annexin V-FITC/PI staining,levels of p53 and Bcl-2 mRNA expression in CDs were determined with RT-PCR,and contents of caspase-3 and caspase-9 proteins were determined by colorimetry.Results:CD apoptosis was induced by SNP at all concentrations tested and in a dose-dependent manner.The SNP concentration of 1 mmol/L and treatment duration of 24 h appeared to be optimal and were selected for the study.Serum samples from the positive control rabbits and from the two higher doses of TGXTC-treated rabbits showed reduction of SNP-induced CD apoptosis,decrease in p53 mRNA expression,inhibition of catalytic activities of caspase-3 and caspase-9,and increase in Bcl-2 mRNA expression when compared with the serum from the blank group(P<0.05).Conclusion:TGXTC-containing sera antagonized SNP-induced CD apoptosis and the molecular basis for the action was associated with up-regulation of Bcl-2, down-regulation of p53 expression,and inhibition of caspase-3 and caspase-9 catalytic activities. | 李西海 吴明霞 叶蕻芝 陈文列 林久茂 郑良朴 刘献祥 | 2011 | Chinese Journal of Integrative Medicine2011，17，6： | 11 |
| 3 | Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice显示文摘Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA. | Jing Xie Jingting Lin Min Wei Yan Teng Qi He Guan Yang Xiao Yang | 2019 | Bone Research2019，7，3： | 8 |
| 4 | Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency显示文摘Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease(KBD) and in an established T-2 toxin-and selenium(Se) deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD. | YANG Hao Jie ZHANG Ying WANG Zhi Lun XUE Sen Hai LI Si Yuan ZHOU Xiao Rong ZHANG Meng FANG Qian WANG Wen Jun CHEN Chen DENG Xiang Hua CHEN Jing Hong | 2017 | Biomedical and Environmental Sciences2017，30，5： | 7 |
| 5 | Anti-inflammatory effects of traditional mixed extract of medicinal herbs(MEMH)on monosodium urate crystal-induced gouty arthritis显示文摘Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis. | Ju-Suk Nam Supriya Jagga Ashish Ranjan Sharma Joon-Hee Lee Jong Bong Park Jun-Sub Jung Sang-Soo Lee | 2017 | Chinese Journal of Natural Medicines2017，15，8： | 6 |
| 6 | THE EXPERIMENTAL STUDY ON THE EFFECTS OF SIX MYCOTOXINS ON THE CULTURAL CHONDROCYTES显示文摘The effects of deoxynlvalenol (DON), T--2 toxin, nivalenol (NIv), hutenolide (BuT).alternariol methyl ether(AME) and monlliformin (cON ) on rabbit articular chondrocytes were observed by using the method of chondrocyte monolayer culture. The amounts or DNA in chondrocytesand glucuronate in matrix were measured. And the chondrocytes were observed by inversion microscope and transmission electron microscope (TEM). The results showed that the cultured chondrocytes were damaged by all the six mycotoxinsl and the synthesis of DNA and the divided reproductionof chondrocytes were restrained; the damage errect was more evident, esl,ecially in the early stage ofculturel the higher concentration or toxin in the media was used, the lower density of the culturalckondrocytes was observed; the cells were even round damaged and dead, so long as the media contolued toxin. When the six mycotoxins arrected the cultural chondrocytes r.spectively, three dirfereut kinds or ultrastructural changes in ckondrocytes were seen by TEa. The relationship betweenmycotoxiu and KBD was preliminarily discussed, and some problems still need further investigation.. | 曹峻岭 熊咏民 李斯纯 郑滨 张矢远 毕华银 莫东旭 | 1998 | Journal of Pharmaceutical Analysis1998，12，1： | 6 |
| 7 | Treatment for cartilage injuries of the knee with a new treatment algorithm显示文摘Treatment of articular cartilage injuries to the knee remains a considerable challenge today. Current procedures succeed in providing relief of symptoms, however damaged articular tissue is not replaced with new tissue of the same biomechanical properties and long-term durability as normal hyaline cartilage. Despite many arthroscopic procedures that often manage to achieve these goals, results are far from perfect and there is no agreement on which of these procedures are appropriate, particularly when full-thickness chondral defects are considered.Therefore, the search for biological solution in long-term functional healing and increasing the quality of wounded cartilage has been continuing. For achieving this goal and apply in wide defects, scaffolds are developed.The rationale of using a scaffold is to create an environment with biodegradable polymers for the in vitro growth of living cells and their subsequent implantation into the lesion area. Previously a few numbers of surgical treatment algorithm was described in reports, however none of them contained one-step or two –steps scaffolds. The ultimate aim of this article was to review various arthroscopic treatment options for different stage lesions and develop a new treatment algorithm which included the scaffolds. | Ahmet ?zmeri? Kadir Bahad?r Alemdaro?lu Nevres Hürriyet Aydo?an | 2014 | World Journal of Orthopedics2014，5，5： | 3 |
| 8 | Protective Effect of Pyrroloquinoline Quinone on TNF-α-induced Mitochondrial Injury in Chondrocytes显示文摘Osteoarthritis(OA)is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity.As a bacterial synthesis of quinine,pyrroloquinoline quinone(PQQ)is a strong redox cofactor with a variety of biological benefits,including antioxidant,anti-inflammation-induced mitochondrial metabolism regulation.This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes.Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α50 ng/mL,TNF-α50 ng/mL+PQQ 10µmol/L for 24 h.Then,morphological study,functional study and mechanism study were taken.The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ,evidenced by elevated number of mitochondria,well-kept mtDNA integrity,preserved ATP level,reestablished mitochondrial membrane potential,and prevented mitochondrial function.The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-αand the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α.PQQ might be a potential chemical for OA intervention. | Guang-tao HAN Wei-song CAI Yu-biao ZHANG Si-qi ZHOU Bin HE Hao-huan LI | 2021 | Current Medical Science2021，41，1： | 3 |
| 9 | The effect of collagen hydrogels on chondrocyte behaviors through restricting the contraction of cell/hydrogel constructs显示文摘Collagen is a promising material for tissue engineering,but the poor mechanical properties of collagen hydrogels,which tend to cause contraction under the action of cellular activity,make its application challengeable.In this study,the amino group of type I collagen(Col I)was modified with methacrylic anhydride(MA)and the photo-crosslinkable methacrylate anhydride modified type I collagen(CM)with three different degrees of substitution(DS)was prepared.The physical properties of CM and Col I hydrogels were tested,including micromorphology,mechanical properties and degradation properties.The results showed that the storage modulus and degradation rate of hydrogels could be adjusted by changing the DS of CM.In vitro,chondrocytes were seeded into these four groups of hydrogels and subjected to fluorescein diacetate/propidium iodide(FDA/PI)staining,cell counting kit-8(CCK-8)test,histological staining and cartilage-related gene expression analysis.In vivo,these hydrogels encapsulating chondrocytes were implanted subcutaneously into nude mice,then histological staining and sulfated glycosaminoglycan(sGAG)/DNA assays were performed.The results demonstrated that contraction of hydrogels affected behaviors of chondrocytes,and CM hydrogels with suitable DS could resist contraction of hydrogels and promote the secretion of cartilage-specific matrix in vitro and in vivo. | Longpeng Dong Qingli Liu Yongli Gao Hengxing Jia Wenling Dai Likun Guo Hongsong Fan Yujiang Fan Xingdong Zhang | 2021 | Regenerative Biomaterials2021，8，4： | 2 |
| 10 | HDAC6 inhibition regulates substrate stiffness-mediated inflammation signaling in chondrocytes显示文摘Osteoarthritis(OA)is a chronic disease and is difficult to cure.Chondrocytes are highly mechanosensitive.Therefore,mechanical therapies have received attention as a therapeutic direction for OA.The stiffness,as a critical cue of the extracellular matrix(ECM),affects cell growth,development,and death.In this study,we use polydimethylsiloxane(PDMS)to create substrates with varying stiffness for chondrocyte growth,interleukin-1β(IL-1β)treatment to mimic the inflammatory environment,and Tubastatin A(Tub A)to inhibit histone deacetylase 6(HDAC6).Our results show that stiff substrates can be anti-inflammatory and provide a better matrix environment than soft substrates.Inhibition of HDAC6 improves the inflammatory environment caused by IL-1βand coordinates with inflammation to spread the chondrocyte area and primary cilia elongation.Without IL-1βand Tub A treatments,the length of the primary cilia rather than frequency is stiffness-dependent,and their length on stiff substrates are greater than that on soft substrates.In conclusion,we demonstrate that stiff substrates,inflammation,and inhibition of HDAC6 enhance the mechanosensitivity of primary cilia and mediate substrate stiffness to suppress inflammation and protect the matrix. | Yang Zhang Godfred K Tawiah Yanjun Zhang Xiaohu Wang Xiaochun Wei Weiyi Chen Xiaohong Qiao Quanyou Zhang | 2023 | Acta Biochimica et Biophysica Sinica2023，55，12： | 1 |
| 11 | The role of mechano growth factor in chondrocytes and cartilage defects:a concise review显示文摘Mechano growth factor(MGF),an isoform of insulin-like growth factor 1(IGF-1),is recognized as a typical mechanically sensitive growth factor and has been shown to play an indispensable role in the skeletal system.In the joint cavity,MGF is highly expressed in chondrocytes,especially in the damaged cartilage tissue caused by trauma or degenerative diseases such as osteoarthritis(OA).Cartilage is an extremely important component of joints because it functions as a shock absorber and load distributer at the weight-bearing interfaces in the joint cavity,but it can hardly be repaired once injured due to its lack of blood vessels,lymphatic vessels,and nerves.MGF has been proven to play an important role in chondrocyte behaviors,including cell proliferation,migration,differentiation,inflammatory reactions and apoptosis,in and around the injury site.Moreover,under the normalized mechanical microenvironment in the joint cavity,MGF can sense and respond to mechanical stimuli,regulate chondrocyte activity,and maintain the homeostasis of cartilage tissue.Recent reports continue to explain its effects on various cell types and sport-related tissues,but its role in cartilage development,homeostasis and disease occurrence is still controversial,and its internal biological mechanism is still elusive.In this review,we summarize recent discoveries on the role of MGF in chondrocytes and cartilage defects,including tissue repair at the macroscopic level and chondrocyte activities at the microcosmic level,and discuss the current state of research and potential gaps in knowledge. | Yi Liu Mengmeng Duan Demao Zhang Jing Xie | 2023 | Acta Biochimica et Biophysica Sinica2023，55，5： | 1 |
| 12 | Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p显示文摘Endochondral bone formation is an important route for bone repair.Although emerging evidence has revealed the functions of long non-coding RNAs(lncRNAs)in bone and cartilage development,the effect of lncRNAs in endochondral bone repair is still largely unknown.Here,we identified a lncRNA,named Hypertrophic Chondrocyte Angiogenesis-related lncRNA(HCAR),and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13(Mmp13)and vascular endothelial growth factorα(Vegfa)in hypertrophic chondrocytes.Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31hiEmcnhi vessels number in a bone repair model.Mechanistically,we proved that lnc-HCAR was mainly enriched in the cytoplasm using fluorescence in situ hybridization(FISH)assay,and it acted as a molecular sponge for miR-15b-5p.Further,in hypertrophic chondrocytes,lnc-HCAR competitively bound to miR-15b-5p to increase Vegfa and Mmp13 expression.Our results proved that lncRNA is deeply involved in endochondral bone repair,which will provide a new theoretical basis for future strategies for promoting fracture healing. | Yun Bai Xiaoshan Gong Rui Dong Zhen Cao Ce Dou Chuan Liu Jianmei Li Fei Kang Jingjin Dai Chunrong Zhao Zhansone Tian Jiulin Tan Qijie Dai Shiwu Dong | 2022 | Genes & Diseases2022，9，2： | 1 |
| 13 | Hydrogel platform with tunable stiffness based on magnetic nanoparticles cross-linked GelMA for cartilage regeneration and its intrinsic biomechanism显示文摘Cartilage injury affects numerous individuals,but the efficient repair of damaged cartilage is still a problem in clinic.Hydrogel is a potent scaffold candidate for tissue regeneration,but it remains a big challenge to improve its mechanical property and figure out the interaction of chondrocytes and stiffness.Herein,a novel hybrid hydrogel with tunable stiffness was fabricated based on methacrylated gelatin(GelMA)and iron oxide nanoparticles(Fe_(2)O_(3))through chemical bonding.The stiffness of Fe_(2)O_(3)/GelMA hybrid hydrogel was controlled by adjusting the concentration of magnetic nanoparticles.The hydrogel platform with tunable stiffness modulated its cellular properties including cell morphology,microfilaments and Young’s modulus of chondrocytes.Interestingly,Fe_(2)O_(3)/GelMA hybrid hydrogel promoted oxidative phosphorylation of mitochondria and facilitated catabolism of lipids in chondrocytes.As a result,more ATP and metabolic materials generated for cellular physiological activities and organelle component replacements in hybrid hydrogel group compared to pure GelMA hydrogel.Furthermore,implantation of Fe_(2)O_(3)/GelMA hybrid hydrogel in the cartilage defect rat model verified its remodeling potential.This study provides a deep understanding of the bio-mechanism of Fe_(2)O_(3)/GelMA hybrid hydrogel interaction with chondrocytes and indicates the hydrogel platform for further application in tissue engineering. | Chenchen Zhou Chunli Wang Kang Xu Zhixing Niu Shujuan Zou Demao Zhang Zhiyong Qian Jinfeng Liao Jing Xie | 2023 | Bioactive Materials2023，，7： | 1 |
| 14 | Click chemistry-based pre-targeting cell delivery for cartilage regeneration显示文摘A fraction of the OA patient population is affected by post-traumatic osteoarthritis(PTOA)following acute joint injuries.Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes,reduced disability,and medical costs.To more effectively treat articular cartilage injury,we have developed a novel cell-based therapy that involves the pretargeting of apoptotic chondrocytes and the delivery of healthy,metabolically active chondrocytes using click chemistry.Specifically,a pre-targeting agent was prepared via conjugating apoptotic binding peptide(ApoPep-1)and trans-cyclooctene(TCO)onto polyethylene glycol(PEG)polymer carrier.The pre-targeting agent would be introduced to injured areas of articular cartilage,leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes.Subsequently,methyltetrazine(Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction.Using an ex vivo human cartilage explant PTOA model,the effectiveness of this new approach was evaluated.Our studies show that this novel approach(Tz-TCO click chemistry)significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes.Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration.The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury. | Cynthia M.Co Samira Izuagbe Jun Zhou Ning Zhou Xiankai Sun Joseph Borrelli Liping Tang | 2021 | Regenerative Biomaterials2021，8，3： | 1 |
| 15 | Conditional disruption of the osterix gene in chondrocytes during early postnatal growth impairs secondary ossification in the mouse tibial epiphysis显示文摘In our previous studies, we have found that the prepubertal increase in thyroid hormone levels induces osterix(Osx) signaling in hypertrophic chondrocytes to transdifferentiate them into osteoblasts. To test if Osx expressed in chondrocytes directly contributes to transdifferentiation and secondary ossification, we generated Osx^flox/flox;Col2-Cre-ERT2 mice and knocked out Osx with a single injection of tamoxifen at postnatal day(P) 3 prior to evaluation of the epiphyseal bone phenotype by μCT, histology, and immunohistochemistry(IHC) at P21. Vehicle(oil)-treated Osx^flox/flox;Col2-Cre-ERT2 and tamoxifen-treated, Cre-negative Osx^flox/flox mice were used as controls.μCT analysis of tibial epiphyses revealed that trabecular bone mass was reduced by 23% in the Osx conditional knockout(c KO) compared with control mice. Trabecular number and thickness were reduced by 28% and 8%,respectively, while trabecular separation was increased by 24% in the c KO mice. Trichrome staining of longitudinal sections of tibial epiphyses showed that bone area and bone area adjusted for total area were decreased by 22% and 18%, respectively. IHC studies revealed the presence of abundant Osx-expressing prehypertrophic chondrocytes in the epiphyses of control mice at P10, but not in the cKO mice. Furthermore, expression levels of MMP13, COL10, ALP, and BSP were considerably reduced in the epiphyses of cKO mice. We also found that Osx overexpression in ATDC5 chondrocytes increased expression of Col10, Mmp13, Alp, and Bsp. Our data indicate that Osx expressed in chondrocytes plays a significant role in secondary ossification by regulating expression of genes involved in chondrocyte hypertrophy and osteoblast transdifferentiation. | Weirong Xing Catrina Godwin Sheila Pourteymoor Subburaman Mohan | 2019 | Bone Research2019，7，3： | 1 |
| 16 | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression显示文摘Osteoarthritis(OA)has been considered non-reversible as articular cartilage wears down with limited repair capacity.Enhanced chondrocyte hypertrophy and increased type X collagen gene(COL10A1)expression have been associated with OA.Therefore,regulators controlling collagen X expression and chondrocyte hypertrophy may play a role in OA intervention.Here,we investigated how Distal-less homeobox 5(DLX5),the distal-less homeobox family member,controls murine Col10a1 gene expression and chondrocyte hypertrophy in chondrogenic cell models and its role in a murine OA model.Through qRT-PCR and Western blot analyses,we detected significantly increased levels of COL10A1 and DLX5 in hypertrophic MCT and ATDC5 cells compared to their proliferative stage.Forced expression of Dlx5 further increases,while knockdown of Dlx5 decreases COL10A1 expression in hypertrophic MCT cells.We have performed dual-luciferase reporter and ChiP assays and demonstrated that DLX5 promotes reporter activity through direct interaction with Col10a1 cis-enhancer.We established a murine OA model and detected markedly increased COL10A1 and DLX5 in the articular cartilage and subchondral bone of the OA mice compared with the controls.Notably,forced overexpression of DLX5 in hypertrophic MCT cells up-regulates RUNX2,and adjacent DLX5 and RUNX2 binding sites have previously been found within the Col10a1 cis-enhancer.Together,our data suggest that DLX5 may cooperate with RUNX2 to control cell-specific Col10a1 expression and chondrocyte hypertrophy and is involved in OA pathogenesis. | Jinnan Chen Fangzhou Chen Xuan Wu Huiqin Bian Chen Chen Xiaojing Zhang Ruoxuan Hei Xiaotong Yang Haochun Yuan Qian Wang Yaojuan Lu Longwei Qiao Qiping Zheng | 2023 | Genes & Diseases2023，10，5： | 1 |
| 17 | A high-resolution route map reveals distinct stages of chondrocyte dedifferentiation for cartilage regeneration显示文摘Articular cartilage damage is a universal health problem.Despite recent progress,chondrocyte dedifferentiation has severely compromised the clinical outcomes of cell-based cartilage regeneration.Loss-of-function changes are frequently observed in chondrocyte expansion and other pathological conditions,but the characteristics and intermediate molecular mechanisms remain unclear.In this study,we demonstrate a time-lapse atlas of chondrocyte dedifferentiation to provide molecular details and informative biomarkers associated with clinical chondrocyte evaluation.We performed various assays,such as single-cell RNA sequencing(scRNA-seq),live-cell metabolic assays,and assays for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),to develop a biphasic dedifferentiation model consisting of early and late dedifferentiation stages.Early-stage chondrocytes exhibited a glycolytic phenotype with increased expression of genes involved in metabolism and antioxidation,whereas late-stage chondrocytes exhibited ultrastructural changes involving mitochondrial damage and stress-associated chromatin remodeling.Using the chemical inhibitor BTB06584,we revealed that early and late dedifferentiated chondrocytes possessed distinct recovery potentials from functional phenotype loss.Notably,this two-stage transition was also validated in human chondrocytes.An image-based approach was established for clinical use to efficiently predict chondrocyte plasticity using stage-specific biomarkers.Overall,this study lays a foundation to improve the quality of chondrocytes in clinical use and provides deep insights into chondrocyte dedifferentiation. | Yishan Chen Yeke Yu Ya Wen Juan Chen Junxin Lin Zixuan Sheng Wenyan Zhou Heng Sun Chengrui An Jiansong Chen Weiliang Wu Chong Teng Wei Wei Hongwei Ouyang | 2022 | Bone Research2022，10，3： | 1 |
| 18 | LOXL3 Inhibits Autophagy of Chondrocytes by Activating Rheb in Osteoarthritis显示文摘Objective This study aimed to investigate the potential mechanisms by which lysyl oxidase like 3(LOXL3)affects the autophagy in chondrocytes in osteoarthritis(OA),specifically through the activation of mammalian target of rapamycin complex 1(mTORC1).Methods To establish an OA model,rats underwent anterior cruciate ligament transection(ACLT).Chondrocytes were isolated from cartilage tissues and cultured.Western blotting was performed to assess the expression of LOXL3,Rheb,phosphorylation of p70S6K(p-p70S6K,a downstream marker of mTORC1),and autophagy markers.The autophagy of chondrocytes was observed using an immunofluorescence assay.Results The expression levels of both LOXL3 and Rheb proteins were upregulated in chondrocytes isolated from the OA model cartilage,in comparison to those from the normal cartilage.The silencing of LOXL3 resulted in a decrease in the protein levels of Rheb and p-p70S6K,as well as an increase in the expression of autophagy-related proteins.Additionally,the effect of LOXL3 could be reversed through the silencing of Rheb.The results of the immunofluorescence assay confirmed the impact of LOXL3 and Rheb on chondrocyte autophagy.Conclusion LOXL3 inhibits chondrocyte autophagy by activating the Rheb and mTORC1 signaling pathways. | Guang-ping ZHENG Chen LIU Liang ZHANG Qiang ZHONG Yun ZHANG Zhong-ming HUANG | 2023 | Current Medical Science2023，43，6： | 0 |
| 19 | Effects of simulated microgravity on the alkaline phosphatase activity and intracellular calcium concentration of cultured chondrocytes显示文摘The effects of simulated microgravity on matrix mineralization of chondrocytes were examined using cultured chicken embryonic chondrocytes as the model. In four days, there was a time course decrease in alkaline phosphatase activity of chondrocytes, a marker of matrix mineralization.Meanwhile, in two days, there was a significant drop in intracellular calcium concentration in contrast to the control. These results indicate that simulated microgravity can suppress matrix calcification of cultured chondrocytes, and intracellular calcium may be involved in the regulation of matrix calcification as the second messenger. | Xiaobing Li Shuzhang Yang Shengguang Li Peidong Jiang Zhihuan Lin | 1999 | Chinese Science Bulletin1999，44，3： | 0 |
| 20 | α-parvin controls chondrocyte column formation and regulates long bone development显示文摘Endochondral ossification requires proper control of chondrocyte proliferation,differentiation,survival,and organization.Here we show that knockout ofα-parvin,an integrin-associated focal adhesion protein,from murine limbs causes defects in endochondral ossification and dwarfism.The mutant long bones were shorter but wider,and the growth plates became disorganized,especially in the proliferative zone.With two-photon time-lapse imaging of bone explant culture,we provide direct evidence showing thatα-parvin regulates chondrocyte rotation,a process essential for chondrocytes to form columnar structure.Furthermore,loss ofα-parvin increased binucleation,elevated cell death,and caused dilation of the resting zones of mature growth plates.Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones(i.e.,resting,proliferative,and hypertrophic zones)of the growth plates.Our results demonstrate a crucial role ofα-parvin in long bone development and shed light on the cellular mechanism through whichα-parvin regulates the longitudinal growth of long bones. | Jifan Yuan Ling Guo Jiaxin Wang Zhongjun Zhou Chuanyue Wu | 2023 | Bone Research2023，11，3： | 0 |
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