1.Exosomes rewire the cartilage microenvironment in osteoarthritis: from intercellular communication to therapeutic strategies.
Yuangang WU ; Jiao LI ; Yi ZENG ; Wenchen PU ; Xiaoyu MU ; Kaibo SUN ; Yong PENG ; Bin SHEN
International Journal of Oral Science 2022;14(1):40-40
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide. However, effective strategies for cartilage repair are lacking, and patients with advanced OA usually need joint replacement. Better comprehending OA pathogenesis may lead to transformative therapeutics. Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior. Specifically, exosome cargos, such as noncoding RNAs (ncRNAs) and proteins, play a crucial role in OA progression by regulating the proliferation, apoptosis, autophagy, and inflammatory response of joint cells, rendering them promising candidates for OA monitoring and treatment. This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA, suggesting new realms to improve OA management.
Apoptosis
;
Cartilage/pathology*
;
Cartilage, Articular/metabolism*
;
Cell Communication
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Chondrocytes/metabolism*
;
Exosomes/pathology*
;
Humans
;
Osteoarthritis/therapy*
2.Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis.
Quan CHEN ; Limin WU ; Cili DAWA ; Bin SHEN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(6):748-757
OBJECTIVE:
To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.
METHODS:
The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.
RESULTS:
Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.
CONCLUSION
The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.
Humans
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Reactive Oxygen Species/metabolism*
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Chondrocytes/metabolism*
;
Osteoarthritis/metabolism*
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Homeostasis
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Mitochondria/metabolism*
;
Cartilage, Articular/metabolism*
3.Intermittent Negative Hydrostatic Pressure and Chondrocyte Metabolism.
Goo Hyun BAEK ; Jun Kyo SUH ; Jong Hwa AHN
The Journal of the Korean Orthopaedic Association 1998;33(4):1199-1205
Experimental findings have suggested that the metabolic activities of articular cartilage can be influenced by mechanical stimuli. Our recent mathematical analysis predicted that cyclic compressive loading may create periods of intermittent negative hydrostatic pressure within the cartilage extracellular matrix. Therefore, we hypothesize that intermittent negative hydrostatic pressure, created in the cartilage extracellular matrix during dynamic compression, has a stimulative effect on the biosynthesis of chondrocytes. In order to test this hypothesis, the present study developed a custom designed negative pressure generator to subject a monolayer culture of chondrocytes to an intermittent negative pressure. It was found that the intermittent negative pressure produced a 40% increase in proteoglycan and a l7% increase in non-collagenous protein synthesis during the pressurization period(p (0.05). The collagenous protein synthesis was not affected by the intermittent negative pressure regimen used in this study. After the intermittent negative pressurization, the metabolic activities of the chondrocytes returned to normal(control level). The intermittent negative pressure also produced an increase in the mRNA signals for aggrecan. Therefore, we conclude that intermittent negative pressure may be one of the major mechanical stimulators of chondrocytes in articular cartilage during dynamic compression.
Aggrecans
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Cartilage
;
Cartilage, Articular
;
Chondrocytes*
;
Collagen
;
Extracellular Matrix
;
Hydrostatic Pressure*
;
Metabolism*
;
Proteoglycans
;
RNA, Messenger
4.The relationship of the expression of estrogen receptor in cartilage cell and osteoarthritis induced by bilateral ovariectomy in guinea pig.
Guofeng, DAI ; Jianmin, LI ; Xinyu, LIU ; Qiaohui, LIU ; Chunmei, LIU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2005;25(6):683-6
To investigate the estrogen receptor (ER) expression in cartilage cell in the development of osteoarthritis induced by bilateral ovariectomy in guinea pig and to find their relationship. 30 two-month-old female guinea pigs were randomly divided into two groups (n = 15 each): sham operation (control) group and ovariectomized group (OVX); Scanning electorne microscope (SEM) and transmission electron microscope (TEM) were obtained to analysis the cartilage degeneration of the hind limb knee joint after 6 and 12 weeks of ovariectomy. Dextran-Coated-Charcoal (DCC) was taken to quantitively detect the expression of ER. The serum levels of estrogen and gestone were detected by immune contest assay. The results showed that ER do exist in the cartilages of the guinea pigs, with higher expression in the control group than in OVX group at the same time point (P < 0.05). It was increased also at 12 th week after operation than that of preoperation. The blood serum levels of estrogen and gestone showed a similar tendency to the expression of ER. Joint cartilage degeneration detected by SEM and TEM could be found at 6 th week, but severe degenerative lesions at 12 th week in the OVX group compared with the control group (P < 0.01). The data suggested that bilateral ovariectomy in guinea pig lead to severe osteoarthritis which mighgt be related to the lower serum level of estrogen and the downregulation of the expression of ER in the cartilage also.
Cartilage, Articular/cytology
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Cartilage, Articular/*metabolism
;
Chondrocytes/metabolism
;
Estrogens/*blood
;
Osteoarthritis/*etiology
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Osteoarthritis/metabolism
;
Ovariectomy
;
Random Allocation
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Receptors, Estrogen/*biosynthesis
;
Receptors, Estrogen/genetics
5.Role of platelet-rich plasma in articular cartilage lesions.
Ming LI ; Junhui ZHANG ; Qunhua JIN ; Jianmin LI ; Zhiyong HE ; Zhenglin DI
Chinese Medical Journal 2014;127(22):3987-3992
6.Normal age-related viscoelastic properties of chondrons and chondrocytes isolated from rabbit knee.
Wang-Ping DUAN ; Zhen-Wei SUN ; Qi LI ; Chun-Jiang LI ; Li WANG ; Wei-Yi CHEN ; Jennifer TICKNER ; Ming-Hao ZHENG ; Xiao-Chun WEI
Chinese Medical Journal 2012;125(14):2574-2581
BACKGROUNDThe mechanical microenvironment of the chondrocytes plays an important role in cartilage homeostasis and in the health of the joint. The pericellular matrix, cellular membrane of the chondrocytes, and their cytoskeletal structures are key elements in the mechanical environment. The aims of this study are to measure the viscoelastic properties of isolated chondrons and chondrocytes from rabbit knee cartilage using micropipette aspiration and to determine the effect of aging on these properties.
METHODSThree age groups of rabbit knees were evaluated: (1) young (2 months, n = 10); (2) adult (8 months, n = 10); and (3) old (31 months, n = 10). Chondrocytes were isolated from the right knee cartilage and chondrons were isolated from left knees using enzymatic methods. Micropipette aspiration combined with a standard linear viscoelastic solid model was used to quantify changes in the viscoelastic properties of chondrons and chondrocytes within 2 hours of isolation. The morphology and structure of isolated chondrons were evaluated by optical microscope using hematoxylin and eosin staining and collagen-6 immunofluorescence staining.
RESULTSIn response to an applied constant 0.3 - 0.4 kPa of negative pressure, all chondrocytes exhibited standard linear viscoelastic solid properties. Model predictions of the creep data showed that the average equilibrium modulus (E(∞)), instantaneous modulus (E(0)), and apparent viscosity (m) of old chondrocytes was significantly lower than the young and adult chondrocytes (P < 0.001); however, no difference was found between young and adult chondrocytes (P > 0.05). The adult and old chondrons generally possessed a thicker pericellular matrix (PCM) with more enclosed cells. The young and adult chondrons exhibited the same viscoelastic creep behavior under a greater applied pressure (1.0 - 1.1 kPa) without the deformation seen in the old chondrons. The viscoelastic properties (E(∞), E(0), and m) of young and adult chondrons were significantly greater than that observed in young and adult cells, respectively (P < 0.001). The adult chondrons were stiffer than the young chondrons under micropipette aspiration (P < 0.001).
CONCLUSIONSOur findings provide a theoretical model to measure the viscoelastic properties of the chondrons as a whole unit by micropipette aspiration, and further suggest that the properties of the chondrocytes and PCM have an important influence on the biomechanical microenvironment of the knee joint cartilage degeneration that occurs with aging.
Aging ; physiology ; Animals ; Cartilage, Articular ; metabolism ; Chondrocytes ; metabolism ; Elasticity ; Rabbits ; Viscosity
7.Changes in the hyaline articular cartilage after air exposure.
Yonsei Medical Journal 1990;31(1):53-59
The changes of hyaline articular cartilage from rabbits after air exposure were evaluated. The knee joints were exposed to air for periods of thirty minutes to two hours. The animals were killed periodically, at three days, one week and three weeks postoperatively. After sacrifice, the cartilage was removed and prepared for study by light microscopy and electron microscopy. Exposure to room air for thirty minutes produced chondrocyte necrosis in the upper third of the cartilage, and exposure for 60 minutes or longer produced chondrocyte necrosis of the entire thickness of articular cartilage at three days after arthrotomy. But, three weeks after arthrotomy, we could not find any chondrocyte necrosis in any rabbits at varying periods of air exposure. There was no significant change in proteoglycan content between the aired and control cartilage. Clinical Relevance: Exposing cartilage to air can cause transient and reversible cartilage damage. If these changes are not reversible, the orthopedic surgeon should consider avoiding the prolonged exposure of articular cartilage to air, since complete matrix disintegration is known to occur months after chondrocyte necrosis.
*Air
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Animal
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Cartilage, Articular/metabolism/*pathology/ultrastructure
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Hyalin/*metabolism
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Microscopy, Electron
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Necrosis
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Rabbits
;
Time Factors
8.Effect of the disruption of three cytoskeleton components on chondrocyte metabolism in rabbit knee cartilage.
Wangping DUAN ; Lei WEI ; Xiaoming CAO ; Heng GUO ; Lei WANG ; ; Yongzhuang HAO ; Xiaochun WEI ;
Chinese Medical Journal 2014;127(21):3764-3770
BACKGROUNDChondrocytes' phenotype and biosynthesis of matrix are dependent on having an intact cytoskeletal structure. Microfilaments, microtubules, and intermediate filaments are three important components of the cytoskeletal structure of chondrocytes. The aims of this study were to determine and compare the effects of the disruption of these three cytoskeletal elements on the apoptosis and matrix synthesis by rabbit knee chondrocytes in vitro.
METHODSChondrocytes were isolated from full-thickness knee cartilage of two-month-old rabbits using enzymatic methods (n = 24). The isolated cells were stabilized for three days and then exposed to low, medium, and high doses of chemical agents that disrupt the three principal cytoskeletal elements of interest: colchicine for microtubules, acrylamide for intermediate filaments, and cytochalasin D for actin microfilaments. A group of control cells were treated with carrier. Early apoptosis was assessed using the Annexin-FITC binding assay by flow cytometry on days 1 and 2 after exposure to the disrupting chemical agents. The components and distribution of the cytoskeleton within the cells were analyzed by laser scanning confocal microscopy (LSCM) with immunofluorescence staining on day 3. The mRNA levels of aggrecan (AGG) and type II collagen (Col-2) and their levels in culture medium were analyzed using real-time PCR and enzyme-linked immunosorbent serologic assay (ELISA) on days 3, 6, and 9.
RESULTSIn the initial drug-dose-response study, there was no significant difference in the vitality of cells treated with 0.1 µmol/L colchicine, 2.5 mmol/L acrylamide, and 10 µg/L cytochalasin D for two days when compared with the control group of cells. The concentrations of colchicine and acrylamide treatment selected above significantly decreased the number of viable cells over the nine-day culture and disrupted significantly more cell nuclei. Real-time PCR and ELISA results showed that the mRNA levels and medium concentrations of AGG and Col-2 were significantly decreased for cultures treated with colchicine and acrylamide when compared with untreated cells at three, six, and nine days, and this inhibition was correlated with higher matrix metalloprotease-13 expression in these cells. Cellular proliferation, monolayer morphology, and matrix metabolism were unaffected in cytochalasin D-treated cells when compared with control cells over the nine-day culture period.
CONCLUSIONSThe disruption of the microtubulin and intermediate filaments induced chondrocyte apoptosis, increased matrix metalloprotease expression, and decreased AGG and Col-2 expression in rabbit knee chondrocyte cultures. Our findings suggest that microtubulin and intermediate filaments play a critical role in the synthesis of cartilage matrix by rabbit knee chondrocytes.
Animals ; Cartilage, Articular ; cytology ; metabolism ; Chondrocytes ; cytology ; Collagen ; metabolism ; Cytoskeleton ; metabolism ; Knee Joint ; cytology ; metabolism ; Microscopy, Confocal ; Rabbits
9.Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice.
Yumei LAI ; Wei ZHENG ; Minghao QU ; Christopher C XIAO ; Sheng CHEN ; Qing YAO ; Weiyuan GONG ; Chu TAO ; Qinnan YAN ; Peijun ZHANG ; Xiaohao WU ; Guozhi XIAO
International Journal of Oral Science 2022;14(1):33-33
The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism*
;
Animals
;
Cartilage, Articular/metabolism*
;
Chondrocytes/pathology*
;
Cytoskeletal Proteins/metabolism*
;
Mice
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Muscle Proteins/metabolism*
;
Osteoarthritis/pathology*
;
Temporomandibular Joint/pathology*
10.Effects of exercises on knee cartilage volume in young healthy adults: a randomized controlled trial.
Chinese Medical Journal 2014;127(12):2316-2321
BACKGROUNDAcute effects of physical exercise on the deformational behavior of knee articular cartilage and changes in cartilage volume are definite. However, conclusive effects of different exercises on the loss of articular cartilage volume have not been proved. In this parallel-group randomized controlled trial, we tested whether 12 weeks of swimming, powerstriding, cycling, and running exercises would decrease the cartilage volume significantly and whether there would be a difference in the loss of cartilage volume after different types of exercises.
METHODSFrom October 2012 to January 2013 we evaluated 120 healthy volunteer students in Biomechanics Laboratory of Tongji University. Body mass index (BMI), right lower limb strength, and right knee cartilage magnetic resonance imaging (MRI) were obtained before exercise. MRI were conducted in East Hospital. The study was approved by Tongji University Ethical Committee, all subjects were randomly assigned to the running, powerstriding, cycling, swimming, and control groups by a drawing of lots. Each group contained 24 samples. At the end of 12 weeks of regular exercises, the same measurement procedures were applied. Cartilage volume was calculated with OSIRIS software based on the quantitative-MRI. Pre- and post-exercise comparisons were carried out using paired t-tests and one-way analysis of variance (ANOVA) was used to compare differences of cartilage volume loss between groups with Student-Newman-Keuls procedure for multiple comparisons.
RESULTSRunning, cycling, and swimming groups resulted in a significant decrease in BMI. The quadriceps peak torque increased significantly in the swimming and cycling groups. Total cartilage volume significantly decreased in the running and cycling groups after 12 weeks of training, without any significant change in the nonimpact swimming, low-impact powerstriding, and control groups. Loss of total cartilage volume in the running and cycling groups were 2.21% (3.03) and 1.50% (0.42).
CONCLUSIONSTwelve weeks of regular physical exercises (i.e., running and cycling) decrease the total knee cartilage volume. Swimming and powerstriding are recommended for the healthy youth. This finding suggests that articular cartilage has the functional adaptation for exercises, and some sports could be the risk factors for the initiation of osteoarthritis (OA) in young healthy adults.
Adolescent ; Adult ; Cartilage, Articular ; metabolism ; physiology ; Exercise ; physiology ; Female ; Humans ; Knee Joint ; metabolism ; physiology ; Male ; Young Adult