Mechanical Chondrocyte Damage Thresholds

2012 ◽  
Author(s):  
Mark C. van Turnhout ◽  
Stefan A. H. de Vries ◽  
Corrinus C. van Donkelaar ◽  
Cees W. J. Oomens
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Mechanical Loading ◽  
Early Stage ◽  
Cartilage Degeneration ◽  
Chondrocyte Apoptosis ◽  
Tissue Volume ◽  
Mechanical Thresholds

Chondrocyte content in articular cartilage is very low. Only 2% to 5% of the tissue volume consists of chondrocytes [1]. Yet, these cells are responsible for maintenance of the tissue. Hence, the loss of chondrocytes that is often occurring at an early stage of cartilage degeneration is detrimental to articular cartilage. Excessive mechanical loading is known to be a cause of cell death. However, mechanical thresholds beyond which chondrocyte apoptosis would be induced are unknown.

Chondrocytes in Agarose: Cell Damage and the Pericellular Matrix

2013 ◽  
Author(s):  
Mark C. van Turnhout ◽  
Stefan A. H. de Vries ◽  
Corrinus C. van Donkelaar ◽  
Cees W. J. Oomens
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Cell Damage ◽  
Adult Life ◽  
Cartilage Degeneration ◽  
Pericellular Matrix ◽  
Repair Capacity

Chondrocytes occupy 2% to 5% of the volume of articular cartilage [1] and are responsible for maintenance of the tissue. In adult life, the healing and repair capacity of chondrocytes is very limited, and the loss of chondrocytes that is often occurring at an early stage of cartilage degeneration is detrimental to articular cartilage. Excessive loading is known to be a cause of cell death.

scholarly journals Wnt/β-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Fengjun Xuan ◽  
Fumiko Yano ◽  
Daisuke Mori ◽  
Ryota Chijimatsu ◽  
Yuji Maenohara ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Cartilage Degeneration ◽  
Mrna Levels ◽  
Superficial Zone ◽  
Gain Of Function ◽  
Wnt Ligands ◽  
Signaling Activation ◽  
Signaling Activity

Abstract Background Both loss- and gain-of-function of Wnt/β-catenin signaling in chondrocytes result in exacerbation of osteoarthritis (OA). Here, we examined the activity and roles of Wnt/β-catenin signaling in the superficial zone (SFZ) of articular cartilage. Methods Wnt/β-catenin signaling activity was analyzed using TOPGAL mice. We generated Prg4-CreERT2;Ctnnb1fl/fl and Prg4-CreERT2;Ctnnb1-ex3fl/wt mice for loss- and gain-of-function, respectively, of Wnt/β-catenin signaling in the SFZ. Regulation of Prg4 expression by Wnt/β-catenin signaling was examined in vitro, as were upstream and downstream factors of Wnt/β-catenin signaling in SFZ cells. Results Wnt/β-catenin signaling activity, as determined by the TOPGAL reporter, was high specifically in the SFZ of mouse adult articular cartilage, where Prg4 is abundantly expressed. In SFZ-specific β-catenin-knockout mice, OA development was significantly accelerated, which was accompanied by decreased Prg4 expression and SFZ destruction. In contrast, Prg4 expression was enhanced and cartilage degeneration was suppressed in SFZ-specific β-catenin-stabilized mice. In primary SFZ cells, Prg4 expression was downregulated by β-catenin knockout, while it was upregulated by β-catenin stabilization by exon 3 deletion or treatment with CHIR99021. Among Wnt ligands, Wnt5a, Wnt5b, and Wnt9a were highly expressed in SFZ cells, and recombinant human WNT5A and WNT5B stimulated Prg4 expression. Mechanical loading upregulated expression of these ligands and further promoted Prg4 transcription. Moreover, mechanical loading and Wnt/β-catenin signaling activation increased mRNA levels of Creb1, a potent transcription factor for Prg4. Conclusions We demonstrated that Wnt/β-catenin signaling regulates Prg4 expression in the SFZ of mouse adult articular cartilage, which plays essential roles in the homeostasis of articular cartilage.

Long Term Effect of P188 on Meniscus Preservation Following Blunt Trauma

2012 ◽  
Author(s):  
Adam C. Abraham ◽  
Megan L. Killian ◽  
Roger C. Haut ◽  
Tammy L. Haut Donahue
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Subsequent Treatment ◽  
Joint Injury ◽  
Secondary Osteoarthritis ◽  
Tissue Degeneration ◽  
Long Term Effect ◽  
Tissue Matrix

Acute knee joint injury has been associated with the development and progression of secondary osteoarthritis (OA). Previous work implicates that acute damage to tissue matrix and cells of the meniscus and articular cartilage may play important roles in early-stage OA [1]. Additionally, it has been shown that articular cartilage matrix repair hinges on chondrocyte preservation [2]. Therefore, inhibition of cell death may halt tissue degeneration. Recently, the FDA-approved surfactant Poloxamer 188 (P-188) has been shown to decrease acute cell death by repair of its plasma membrane, as well as mediate p38 signaling and subsequent inflammatory and apoptotic signaling leading to a reduction in degeneration of impacted cartilage [3, 4]. Therefore, it was hypothesized that matrix glycosaminoglycans of the meniscus will be preserved in the long-term following traumatic impaction and subsequent treatment with P-188.

scholarly journals Chondrocytes apoptosis in osteoarthritis

2018 ◽  
Vol 72 ◽  
pp. 875-883
Author(s):  
Sabina Galiniak ◽  
Izabela Krawczyk-Marć ◽  
Agata Wawrzyniak ◽  
Stanisław Orkisz
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Mechanical Damage ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Free Oxygen Radicals ◽  
Motor Disability ◽  
Chondrocyte Death ◽  
Underlying Causes

Osteoarthritis (OA) is a type of degenerative joint disease where the balance between the degradation and the regeneration of articular cartilage is impaired, which leads to its progressive loss. This disease is the most common chronic musculoskeletal disease that leads to premature motor disability. Risk factors for developing OA include age, obesity, sex, past traumas and arthritis, genetic factors, diet and ethnicity. Typical OA symptoms are arthralgia, restriction of movement, cracking and secondary inflammatory lesions. In recent years, the underlying causes of this disease include chondrocyte death by apoptosis, necrosis or combinations of these types of cell death. Apoptosis, called programmed cell death, has clear morphological features, and is a highly regulated process. Apoptosis is involved in maintaining homeostasis; however, its severity is observed in many pathological conditions. Articular cartilage chondrocyte death by apoptosis disrupts the proper maintenance of cartilage structure by reducing cell density. Chondrocyte apoptosis causes mechanical damage, manifested by increased synthesis of free oxygen radicals and disturbance of the integrity of the extracellular matrix. An increasing amount of reports regarding the potential pharmacological substances that have been used as inhibitors of apoptosis have improved the quality of life in OA patients. This article presents the current state of knowledge on apoptosis and apoptotic death of chondrocytes in the course of osteoarthritis.

scholarly journals Reduction of knee joint load suppresses cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis using a post-traumatic rat model

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254383
Author(s):  
Ikufumi Takahashi ◽  
Keisuke Takeda ◽  
Taro Matsuzaki ◽  
Hiroshi Kuroki ◽  
Masahiro Hoso
Keyword(s):  
Articular Cartilage ◽  
Knee Joint ◽  
Rat Model ◽  
Early Stage ◽  
Cartilage Degeneration ◽  
Male Rats ◽  
Hindlimb Suspension ◽  
Osteophyte Formation ◽  
Post Traumatic ◽  
Joint Load

The purpose of this study was to clarify the histological effect of reducing the loading to knee on cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis (OA) using a post-traumatic rat model. Ten male rats were randomly allocated into two experimental groups: OA induction by surgical destabilization of medial meniscus (DMM, OA group) and hindlimb suspension after OA induction by DMM (OAHS group). The articular cartilage, osteophyte formation, and synovial membrane in the medial tibiofemoral joint were analyzed histologically and histomorphometrically at 2 and 4 weeks after surgery. The histological scores and changes in articular cartilage and osteophyte formation were significantly milder and slower in the OAHS group than in the OA group. At 2 and 4 weeks, there were no significant differences in cartilage thickness and matrix staining intensity between both the groups, but chondrocytes density was significantly lower in the OA group. Synovitis was milder in OAHS group than in OA group at 2 weeks. Reducing knee joint loading inhibited histological OA changes in articular cartilage, osteophyte formation, and synovial inflammation. This result supports the latest clinical guidelines for OA treatment. Further studies using biochemical and mechanical analyses are necessary to elucidate the mechanism underlying delayed OA progression caused by joint-load reduction.

scholarly journals Continuous infusion of dexamethasone aggravates the damage of cartilage via upregulating p-AKT and impairing articular autophagy in experimental OA model

2020 ◽  
Author(s):  
liang chen ◽  
Zhenhong Ni ◽  
Jinfan Zhang ◽  
Junlan Huang ◽  
Yangli Xie ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Continuous Infusion ◽  
Late Stage ◽  
Early Stage ◽  
Cartilage Matrix ◽  
Chondrocyte Apoptosis ◽  
Western Blot Assay ◽  
Akt Activation

Abstract Objective To explore the effect of dexamethasone (Dex) infusion on articular cartilage and the underlying mechanisms in vitro and in vivo. Methods Destabilization of medial meniscus (DMM)-induced OA mouse model was used in this study. The mice with Dex treatment were sacrificed and then the knee joint samples were obtained for pathological analysis. Mouse primary chondrocytes were isolated and cultured in the presence or absence of Dex, which were used for calcification analysis and western blot assay. Results Dex accelerated the loss of articular cartilage matrix in mice, while it aggravated the damage of cartilage in DMM-induced OA model at the late stage. The calcium content in calcified cartilage layer in the joints from Dex treated OA mice was significantly higher than that from control mice. Dex treatment enhanced mineralization of articular cartilage matrix and leaded to massive apoptosis of chondrocytes in OA model. In addition, Dex caused autophagy of chondrocytes in the early stage, which was decreased at the late stage of Dex treatment. Moreover, we found that the effect of Dex on the mineralization of articular cartilage matrix in mice was related to AKT activation. Conclusions Continuous infusion of Dex can enhance the calcification of cartilage via AKT activation and increase chondrocyte apoptosis through inhibiting autophagy, which aggravates the damage of articular cartilage and accelerates the progression of OA in vivo.

scholarly journals MiR-34a Enhances Chondrocyte Apoptosis, Senescence and Facilitates Development of Osteoarthritis by Targeting DLL1 and Regulating PI3K/AKT Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 1304-1316 ◽  
Author(s):  
Wei Zhang ◽  
Peichun Hsu ◽  
Biao  Zhong ◽  
Shang Guo ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Target Genes ◽  
Cartilage Degeneration ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Chondrocyte Apoptosis ◽  
Articular Chondrocyte ◽  
Reporter System ◽  
Chondrocyte Death

Background/Aims: Osteoarthritis (OA) is the prevalent degenerative disease caused by various factors. MicroRNAs are important regulators in the inflammation and immune response. The aim of this study was to investigate the effect of microRNA-34a (MiR-34a) on the death of chondrocytes, senescence, as well as its role in OA progression. Methods: A series of experiments involving CCK-8, flow cytometry, β-galactosidase staining and wound healing assays were conducted to determine the cellular capabilities of proliferation, cell apoptosis, senescence and the ability of cells to recover from injury, respectively. Binding sites between miR-34a and delta-like protein 1 (DLL1) were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. OA model was generated via surgery. Results: We found that miR-34a expression was increased in the cartilage of OA patients. In rat chondrocytes and chondrosarcoma cells, miR-34a transfections noticeably inhibited the expression of DLL1, triggered cell death and senescence, suppressed proliferation, and prevented scratch assay wound closure. However, transfection of a miR-34a inhibitor displayed adverse effects. Additionally, secretion and expression of factors associated with cartilage degeneration were altered via miR-34a. Moreover, miR-34a directly inhibits DLL1 mRNA. Furthermore, concentrations of DLL1, total PI3K, and p-AKT declined in chondrocytes that overexpress miR-34a. DLL1 overexpression elevated PI3K and p-AKT levels, and eliminated cell death triggered by a miR-34a mimic. In vivo, miR-34a remarkably inhibited miR-34a up-regulation, while enhanced the level of DLL1 expression. In the knee joints of surgery-induced OA rats, articular chondrocyte death and loss of cartilage were attenuated via miR-34a antagomir injection. Conclusions: These findings indicate that miR-34a contributes to chondrocyte death, causing OA progression through DLL1 and modulation of the PI3K/AKT pathway.

The Effect of Total Meniscectomy versus Caudal Pole Hemimeniscectomy on the Stifle Joint of the Sheep

1999 ◽  
Vol 12 (02) ◽  
pp. 56-63 ◽  
Author(s):  
C. R. Bellenger ◽  
P. Ghosh ◽  
Y. Numata ◽  
C. Little ◽  
D. S. Simpson
Keyword(s):  
Tissue Culture ◽  
Articular Cartilage ◽  
Fibrous Tissue ◽  
Cartilage Degeneration ◽  
Medial Compartment ◽  
Proteoglycan Synthesis ◽  
Stifle Joint ◽  
Medial Meniscectomy ◽  
Tibial Condyle ◽  
Articular Cartilage Degeneration

SummaryTotal medial meniscectomy and caudal pole hemimeniscectomy were performed on the stifle joints of twelve sheep. The two forms of meniscectomy produced a comparable degree of postoperative lameness that resolved within two weeks of the operations. After six months the sheep were euthanatised and the stifle joints examined. Fibrous tissue that replaced the excised meniscus in the total meniscectomy group did not cover as much of the medial tibial condyle as the residual cranial pole and caudal fibrous tissue observed following hemimeniscectomy. The articular cartilage from different regions within the joints was examined for gross and histological evidence of degeneration. Analyses of the articular cartilage for water content, glycosaminoglycan composition and DNA content were performed. The proteoglycan synthesis and release from explanted articular cartilage samples in tissue culture were also measured. There were significant pathological changes in the medial compartment of all meniscectomised joints. The degree of articular cartilage degeneration that was observed following total meniscectomy and caudal pole meniscectomy was similar. Caudal pole hemimeniscectomy, involving transection of the meniscus, causes the same degree of degeneration of the stifle joint that occurs following total meniscectomy.The effect of total medial meniscectomy versus caudal pole hemimeniscectomy on the stifle joint of sheep was studied experimentally. Six months after the operations gross pathology, histopathology, cartilage biochemical analysis and the rate of proteoglycan synthesis in tissue culture were used to compare the articular cartilage harvested from the meniscectomised joints. Degeneration of the articular cartilage from the medial compartment of the joints was present in both of the groups. Caudal pole hemimeniscectomy induces a comparable degree of articular cartilage degeneration to total medial meniscectomy in the sheep stifle joint.

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