C10orf10/DEPP activates mitochondrial autophagy and maintains chondrocyte viability in the pathogenesis of osteoarthritis

2022 ◽  
Vol 36 (2) ◽  
Author(s):  
Masanari Kuwahara ◽  
Yukio Akasaki ◽  
Ichiro Kurakazu ◽  
Takuya Sueishi ◽  
Masakazu Toya ◽  
...  
2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.


2021 ◽  
Vol 50 (3) ◽  
pp. 633-640
Author(s):  
Roger Rengert ◽  
Darren Snider ◽  
Peter J. Gilbert

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Yang Wang ◽  
Xiang-Yun Jin ◽  
Yu-Hui Ma ◽  
Wei-Jie Cai ◽  
Wei-Yuan Xiao ◽  
...  

Abstract Background Cartilage injury and pathological degeneration are reported in millions of patients globally. Cartilages such as articular hyaline cartilage are characterized by poor self-regeneration ability due to lack of vascular tissue. Current treatment methods adopt foreign cartilage analogue implants or microfracture surgery to accelerate tissue repair and regeneration. These methods are invasive and are associated with the formation of fibrocartilage, which warrants further exploration of new cartilage repair materials. The present study aims to develop an injectable modified gelatin hydrogel. Method The hydrogel effectively adsorbed proteoglycans secreted by chondrocytes adjacent to the cartilage tissue in situ, and rapidly formed suitable chondrocyte survival microenvironment modified by ε-poly-L-lysine (EPL). Besides, dynamic covalent bonds were introduced between glucose and phenylboronic acids (PBA). These bonds formed reversible covalent interactions between the cis−diol groups on polyols and the ionic boronate state of PBA. PBA-modified hydrogel induced significant stress relaxation, which improved chondrocyte viability and cartilage differentiation of stem cells. Further, we explored the ability of these hydrogels to promote chondrocyte viability and cartilage differentiation of stem cells through chemical and mechanical modifications. Results In vivo and in vitro results demonstrated that the hydrogels exhibited efficient biocompatibility. EPL and PBA modified GelMA hydrogel (Gel-EPL/B) showed stronger activity on chondrocytes compared to the GelMA control group. The Gel-EPL/B group induced the secretion of more extracellular matrix and improved the chondrogenic differentiation potential of stem cells. Finally, thus hydrogel promoted the tissue repair of cartilage defects. Conclusion Modified hydrogel is effective in cartilage tissue repair.


Author(s):  
Nadeen O. Chahine ◽  
Nicole M. Collette ◽  
Heather Thompson ◽  
Gabriela G. Loots

Carbon nanotubes (CNTs) are cylindrical allotropes of carbon that are nanometers in diameter and posses unique physical properties, positioning them as ideal materials for studying physiology at a single cell level. CNTs have the potential to become a very important component of medical therapeutics, likely acting as (a) drug delivery system [1], (b) existing as an interfacial layer in surgical implants [2,3], or (c) acting as scaffolding in tissue engineering [4,8]. While some studies have explored the use of CNTs as a novel material in regenerative medicine, they have not yet been fully evaluated in cellular systems. One major limitation of CNTs that must be overcome is their inherent cytotoxicity. The goal of this study is to assess the long-term biocompatibility of CNTs for chondrocyte growth. We hypothesize that CNT-based material in tissue engineering can provide an improved molecular sized substrate for stimulation of cellular growth, and structural reinforcement of the scaffold mechanical properties. Here we present data on the effects of CNTs on chondrocyte viability and biochemical deposition examined in composite materials of hydrogels + CNTs mixtures. Also, the effects of CNTs surface functionalization with polyethlyne glycol (PEG) or carboxyl groups (COOH) were examined.


2006 ◽  
Vol 67 (8) ◽  
pp. 1280-1285 ◽  
Author(s):  
Beth Rauch ◽  
Ryland B. Edwards ◽  
Yan Lu ◽  
Zhengling Hao ◽  
Peter Muir ◽  
...  

2019 ◽  
Vol 12 (4) ◽  
pp. 169-178
Author(s):  
Pudkrong Kaewpichit ◽  
Somrat Charuluxananan ◽  
Monpichar Srisa-Art ◽  
Sarocha Sisawat ◽  
Vitavat Aksornkitti ◽  
...  

AbstractBackgroundIntra-articular injections of local anesthetics are used commonly in articular surgery. However, chondrocyte viability and metabolism may be adversely affected by various anesthetics.ObjectivesTo assess the chondrotoxic effects of bupivacaine, levobupivacaine, and ropivacaine on human chondrocytes and elucidate possible mechanisms of chondrocyte death.MethodsCultured human chondrocytes (CHON-001) were exposed to 0.25% or 0.5% of bupivacaine, levobupivacaine, and ropivacaine in vitro. Cell viability was determined by flow cytometry after 15, 30, 60, and 120 min of exposure. Chondrocyte reactive oxygen species (ROS) production was measured every 10 min for up to 1 h using 2ʹ,7ʹ-dichlorodihydrofluorescein staining. Chondrocyte production of glycosaminoglycan was measured by capillary electrophoresis. NO production was measured using a colorimetric assay kit.ResultsWe found a significant increase in chondrotoxicity dependent on exposure time and concentration of the anesthetic. At 60 min, chondrocyte viability was significantly (P < 0.05) decreased when exposed to 0.5% levobupivacaine (32.5%), or 0.25% or 0.5% bupivacaine (34.3% or 46.5%, respectively) compared with exposure to phosphate-buffered saline (PBS) vehicle as a control. Cell death at 120 min was mainly necrosis. There was no difference in viability after treatment with either concentration (0.25% or 0.5%) of ropivacaine at any time compared with exposure to PBS. We found increased production of NO, while ROS decreased after exposure to any of the anesthetics tested.ConclusionsRopivacaine may be safer than bupivacaine or levobupivacaine as an intra-articular analgesic. Chondrotoxicity of anesthetics in vitro may be mediated via a reactive nitrogen species-dependent pathway.


2008 ◽  
Vol 58 (4) ◽  
pp. 1076-1085 ◽  
Author(s):  
Shuhei Otsuki ◽  
Diana C. Brinson ◽  
Lilo Creighton ◽  
Mitsuo Kinoshita ◽  
Robert L. Sah ◽  
...  

2010 ◽  
Vol 19 (04) ◽  
pp. 265-272 ◽  
Author(s):  
Andrew Pennock ◽  
Ferdinand Wagner ◽  
Catherine Robertson ◽  
Frederick Harwood ◽  
William Bugbee ◽  
...  

2019 ◽  
Vol 20 (4) ◽  
pp. 545-555
Author(s):  
Jianhong Qi ◽  
Chao Jin ◽  
Pengwei Qu ◽  
Lu Zhou ◽  
Di Xie ◽  
...  

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