Mechanostimulation changes the catabolic phenotype of human dedifferentiated osteoarthritic chondrocytes

Halbwirth, Florian; Niculescu‐Morzsa, Eugenia; Zwickl, Hannes; Bauer, Christoph; Nehrer, Stefan

doi:10.1007/s00167-014-3412-8

Cited by 18 publications

(16 citation statements)

References 52 publications

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“…IL-6 expression directly contributes to the inhibitory effect of aggrecan through the Notch receptor [ 33 ], mediating induction of MMP-13 expression [ 34 ]. MMP-13 is a catabolic factor for cartilage ECM metabolism, degrading proteoglycans and type II collagen [ 35 , 36 ]. Aucubin has been shown to inhibit TNF-alpha and IL-6 production in antigen-stimulated rat basophilic leukemia-2H3 mast cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

Young

Chuang

Hsu

et al. 2017

BMC Complement Altern Med

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BackgroundDuring the onset of osteoarthritis (OA), certain biochemical events have been shown to accelerate cartilage degradation, including the dysregulation of cartilage ECM anabolism, abnormal generation of reactive oxygen species (ROS) and overproduction of proteolytic enzymes and inflammatory cytokines. The potency of aucubin in protecting cellular components against oxidative stress, inflammation and apoptosis effects are well documented, which makes it a potential candidate for OA treatment. In this study, we aimed to evaluate the protective benefits of aucubin against OA using H2O2 and compression induced OA-like chondrocyte models.MethodsThe effects of aucubin were studied in porcine chondrocytes after 1 mM H2O2 stimulation for 30 min or sustained compression for 24 h. Effects of aucubin on cell proliferation and cytotoxicity of chondrocytes were measured with WST-1 and LDH assays. ROS production was evaluated by the Total ROS/Superoxide Detection Kit. Caspase-3 activity was evaluated by the CaspACE assay system. The levels of apoptosis were evaluated by the Annexin V-FITC apoptosis detection kit. OA-related gene expression was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Total DNA quantification was evaluated by the DNeasy Blood and Tissue kit. Sulfated-glycosaminoglycans (sGAGs) production and content were evaluated by DMMB assay and Alcian blue staining.ResultsThe results showed that the ROS scavenge effects of aucubin appeared after 1 h of pretreatment. Aucubin could reduce the caspase-3 activity induced by H2O2, and reduced the apoptosis cell population in flowcytometry. In RT-qPCR results, aucubin could maintain ACAN and COL2A1 gene expressions, and prevent IL6 and MMP13 gene up-regulation induced by H2O2 and compression stimulations. In the DMMB assay and Alcian blue staining, aucubin could maintain the sGAG content and protect chondrocytes against compressive stress, but not oxidative stress from H2O2.ConclusionsThese results indicated that aucubin has protective effects in an osteoarthritic chondrocyte model induced by H2O2 and mechanical stimulus.

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Section: Discussionmentioning

confidence: 99%

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

Young

Chuang

Hsu

et al. 2017

BMC Complement Altern Med

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“…However, conflicting results regarding the ability of mechanical stimulation to alter cartilage, or trabecular bone structure, in animal models and clinical studies, have recently been reported. Previous in vitro studies suggest that mid-term intermittent mechanical stimulation (cycles of 1-h sinusoidal stimulation [1 Hz] and a 4-h break; maximum compression, 2.5%) in vitro has the potential to improve the quality of cellular matrix constructs prepared from dedifferentiated osteoarthritic chondrocytes [27]. Tsuang Y-H et.al proved that mechanical stimulation (10% scaffold thickness 1-Hz amplitude lasting for 24 h) could enhance matrix protein accumulation in cultured chondrocytes [28].…”

Section: Discussionmentioning

confidence: 99%

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

Wang

Liu

Chen³

et al. 2017

BMC Musculoskelet Disord

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BackgroudWhole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)–induced knee osteoarthritisrabbit model.MethodNinety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.ResultsAfter 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.ConclusionOur data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

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“…Recently, several attempts have been made to prevent the dedifferentiation of chondrocytes, thereby enhancing the efficiency of ACT. 11, 29, 30 In addition, several growth factors or cytokines can enhance the redifferentiation of dedifferentiated chondrocytes, accompanied by ECM formation. 31, 32, 33 Nonetheless, the short half-life and high cost of cytokines restrict their use in ACT.…”

Section: Discussionmentioning

confidence: 99%

AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-β signal

Ahn

Kumar

et al. 2016

Cell Death Dis

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Dedifferentiation and degeneration of chondrocytes critically influences the efficiency of cartilage repair. One of the causes is the defect of transforming growth factor (TGF)-β signaling that promotes chondrogenic differentiation and degeneration. In the present study, we found that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) negatively regulates TGF-β signaling via interactions with Smad2 and Smad3 in immunoprecipitation assay and luciferase assay. In addition, we observed that the AIMP1 expression level was significantly increased in osteoarthritis (OA) patient-derived degenerated chondrocytes compared with healthy control. So, we hypothesized that downregulation of AIMP1 using small-interfering RNA (siRNA) technology in dedifferentiated (collected at passage #6) and degenerated (obtained from OA-affected areas) chondrocytes could lead to recover TGF-β signaling in both chondrocytes. Indeed, AIMP1 downregulation restored TGF-β signaling by promoting phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics in both dedifferentiated and degenerated chondrocytes. Additionally, implantation analyses using in vivo mouse model clearly showed that AIMP1 downregulation resulted in the increased chondrogenic potential as well as the enhanced cartilage tissue formation in both dedifferentiated and degenerated chondrocytes. Histological analyses clarified that AIMP1 downregulation increased expression levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken together, these data indicate that AIMP1 downregulation using siRNA is a novel tool to restore TGF-β signaling and thereby increases the chondrogenic potential of dedifferentiated/degenerated chondrocytes, which could be further developed as a therapeutic siRNA to treat OA.

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Mechanostimulation changes the catabolic phenotype of human dedifferentiated osteoarthritic chondrocytes

Cited by 18 publications

References 52 publications

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-β signal

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