Increase in NO causes osteoarthritis and chondrocyte apoptosis and chondrocyte ERK plays a protective role in the process

Chen, Qun; Kao, Xibin; Chen, Jinghong; Dong, Zhaoheng; Chen, Chen

doi:10.1007/s11033-021-06731-0

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…Fortunately, we observed potent antiapoptotic effect in chondrocytes followed by daphnoretin treatment. Moreover, daphnoretin abated the IL-1β-induced production of PGE2, NO, TNF-α and IL-6, which are all involved in chondrocyte apoptosis and cell viability decline [31][32][33][34]. In vivo experiments showed that daphnoretin alleviated the pathological injury of the knee joint in OA mice.…”

Section: Discussionmentioning

confidence: 92%

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

Zhou¹,

Wang

2022

J Orthop Surg Res

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Background Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA. Methods The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1β (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin–eosin (H&E) staining and safranin O-fast green staining. Results Daphnoretin effectively choked IL-1β-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1β-induced chondrocytes. What’s more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS. Conclusion Daphnoretin alleviated IL-1β-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome. Graphical abstract

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Section: Discussionmentioning

confidence: 92%

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

Zhou¹,

Wang

2022

J Orthop Surg Res

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“…22 Pre-vious studies have suggested that low concentrations of NO protect cells from apoptosis, whereas excessive NO induces apoptosis. 23,24 The antiapoptotic mechanism can be the regulation of protective genes such as Bcl-2 as well as direct inhibition of the apoptotic caspase family. 25,26 Except for the ability of L-arg to regulate apoptosis, L-arg has also been reported to promote the proliferation of osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…As a basic substrate of NO, L‐arg generates NO under the action of nitric oxide synthase (NOS) and subsequently regulates apoptosis 22 . Previous studies have suggested that low concentrations of NO protect cells from apoptosis, whereas excessive NO induces apoptosis 23,24 . The antiapoptotic mechanism can be the regulation of protective genes such as Bcl‐2 as well as direct inhibition of the apoptotic caspase family 25,26 .…”

Section: Discussionmentioning

confidence: 99%

L‐arginine protects cementoblasts against hypoxia‐induced apoptosis through Sirt1‐enhanced autophagy

Tan

Bai

et al. 2022

Journal of Periodontology

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Background L‐arginine (L‐arg) can reduce apoptosis in a variety of cells. Cementoblast apoptosis is related to root resorption during orthodontic treatment. In the present study, we aimed to study the regulatory effect and potential mechanism of L‐arg on cementoblast apoptosis and root resorption. Methods The apoptosis‐related mRNA and protein expression of murine cementoblast (OCCM‐30) was assessed after L‐arg treatment. To investigate the role of Sirtuin 1 (Sirt1) and autophagy in L‐arg resistance to cementoblast apoptosis and root absorption, resveratrol, and EX527 were used to activate or inhibit Sirt1, and chloroquine (CQ) was used to inhibit autophagy. Results In vitro, L‐arg inhibited hypoxia‐induced apoptosis in OCCM‐30. Further, L‐arg increased Sirt1 expression whereas Sirt1 suppression by EX527 reversed the inhibitory effect of L‐arg on cell apoptosis. Sirt1 activator resveratrol increased the ratio of microtubule‑associated protein light chain 3 (LC3) II/I and decreased the expression of SQSTM1/p62 (p62), suggesting autophagy activation. Autophagy enhancement could reduce apoptosis. Caspase‐3 and Bax expression was decreased, and Bcl‐2 expression was increased. When autophagy was inhibited by CQ, the positive effects of Sirt1 were attenuated. In vivo, L‐arg application reduced root resorption in rats, as demonstrated by decreased root absorption volume. Similarly, L‐arg upregulated Sirt1, which activated autophagy in the root resorption model, and less root resorption was observed in the Sirt1 activation group. Conclusion L‐arg reduced cementoblast apoptosis in hypoxia and reduced root resorption induced by loading force in rats, which may be partly mediated by Sirt1‐enhanced autophagy.

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“…The release of proinflammatory factors can contribute to the induction of NO synthesis by NO synthase, inhibit chondrocyte proliferation, and reduce the synthesis of the extracellular matrix. At the same time, NO can also directly damage the vascular wall, increase the permeability of the vascular wall and cause synovial congestion and edema and leukocyte exudation (52). TNF-a, as a common inflammatory mediator, can act alone or synergistically with other cytokines such as IL-1b and IL-6 to stimulate the production of cartilage, and synovial and subchondral bone layer-associated cells to produce matrix metalloproteinases, leading to gradual loss of cartilage collagen and proteoglycan and inhibition of proteoglycan and type II collagen synthesis, indirectly causing chondrocyte death and disrupting the homeostatic balance between cartilage damage and repair, which results in varying degrees of cartilage lysis and damage (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis

et al. 2022

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AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

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Increase in NO causes osteoarthritis and chondrocyte apoptosis and chondrocyte ERK plays a protective role in the process

Cited by 5 publications

References 35 publications

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

L‐arginine protects cementoblasts against hypoxia‐induced apoptosis through Sirt1‐enhanced autophagy

Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis

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