Open Access

Changes of type II collagenase biomarkers on IL‑1β‑induced rat articular chondrocytes

Corrigendum in: /10.3892/etm.2023.12040

  • Authors:
    • Xiangying Ma
    • Zhiheng Zhang
    • Meilun Shen
    • Yuanqiang Ma
    • Rouqian Li
    • Xiaodi Jin
    • Li Gao
    • Zhi Wang
  • View Affiliations

  • Published online on: April 2, 2021     https://doi.org/10.3892/etm.2021.10014
  • Article Number: 582
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is characterized by progressive degeneration of cartilage, formation of cartilage at the cartilage edge, and remodeling of the subchondral bone. Pro‑inflammatory cytokines [e.g., interleukin (IL)‑1β] that induce inflammation and promote chondrocyte damage induce OA. Currently, the diagnosis of OA is commonly based on imaging examinations (e.g., X‑ray) and evaluations of clinical symptoms; however, biomarkers that can effectively diagnose OA are currently not available. By studying the mechanism underlying OA cartilage injury and changes in the concentrations of the biomarkers procollagen type II carboxy‑terminal propeptide (PIICP), collagen type‑II C‑telopeptide fragments (CTX‑II), and type II collagen cleavage neoepitope (C2C) during pathogenesis, the present study established a theoretical basis for the evaluation and early diagnosis of OA. In an experiment, 10 ng/ml IL‑1β was used to the treat chondrocyte‑induced OA models in vitro for 0, 12, 24 and 48 h. Western blotting was used to detect the expression levels of matrix metalloproteinase (MMP)‑3, MMP‑13, and inducible nitric oxide synthase (iNOS) protein at each time‑point. The concentrations of CTX‑II, C2C, and PIICP in the cell culture supernatant were detected by ELISA kit. A biochemical kit was used to detect changes of nitric oxide (NO) in the cell culture supernatant. In addition, chondrocytes were treated with 10 ng/ml IL‑1β for 0, 30, 60 and 90 min and the translocation and phosphorylation of the NF‑κB pathway were investigated by western blotting. Following IL‑1β stimulation, the NF‑κB pathway was activated to increase the expression levels of MMPs and iNOS synthesis downstream of the pathway, resulting in an increased degradation of type II collagen (Col II). To sum up, pro‑inflammatory IL‑1β induced an OA chondrocyte model. During the development of OA, the expression of MMPs and NO increased and Col II was degraded.

Introduction

Osteoarthritis (OA) is one of the most common arthritic diseases (1) and a major cause of chronic pain and dysfunction in patients. OA is a chronic degenerative disease that is characterized by joint disease, cartilage degeneration and erosion, fibrosis, and osteophyte formation. In the worst cases, OA leads to pain and disability and severely affects the quality of life of patients (2-4). However, the origins and causes of OA have not been fully elucidated to date.

Chondrocytes are the only type of cell present in articular cartilage, where they are responsible for maintaining the normal synthesis and renewal of the cartilage matrix (4). A previous study associated pro-inflammatory cytokines [e.g., interleukin (IL)-1β] with OA pathogenesis and revealed that it plays a pivotal role in OA (3). The activation of inflammation-related signaling pathways was revealed to be initiated by IL-1β. Then, IL-1β stimulated the expression of matrix metalloproteinases (MMPs) and nitric oxide (NO), which resulted in the destruction of the cartilage matrix (5). MMP-3 and MMP-13 have been recognized as the two most important collagenases that are involved in the degradation of the cartilage matrix; these are also crucial factors in OA (6,7). It has been revealed that the expression levels of MMP-3 and MMP-13 are increased in synovial fluid from patients with OA (8). The overexpression of metalloproteinases promotes degradation of type II collagen (Col II) (4).

Col II is the main component of the extracellular matrix (ECM) (4). The fibrillar Col II is the major collagen of articular cartilage, and includes both procollagen with both amino (N)-terminal (PIINP and PIIANP) and carboxy (C)-terminal propeptide (PIICP) (9). The PIICP levels have been correlated with the progression of OA in the knee (10). When Col II breaks down and produces fragments, such as collagenase, type II collagen cleavage neoepitope (C2C) and collagen type-II C-telopeptide fragments (CTX-II) are generated (11,12). C2C is a useful biomarker that reflects the cleavage of Col II in OA and the levels of CTX-II have been demonstrated to be associated with the total damage of osteophytes (13).

Numerous studies have revealed that IL-1β can activate the nuclear factor-κB (NF-κB) pathway (14-16). NF-κB has been identified as an inducible transcription factor (17) and the NF-κB pathway has been reported to regulate the balance in the catabolism that controls numerous inflammation-related genes (18). When NF-κB has been stimulated by IL-1β, inactive NF-κB becomes active and translocates from the cytoplasm to the nucleus; moreover, the phosphorylation of p65 is translated into the nucleus and the expression of downstream genes is increased (14,19). Therefore, OA is associated with inflammation, and reducing activation of the NF-κB pathway may be a therapeutic strategy for the treatment of OA.

As a class of molecules with high sensitivity, biomarkers associated with OA have been extensively studied and have broad application prospects (20). However, in previous studies, chondrocytes induced with 1 ng/ml IL-1α or 10 ng/ml IL-1β to simulate an in vitro OA model mostly focused on a single marker at a certain time-point (21,22), while not studying the change trend of these markers in OA, and thus, not reflecting OA progression. In the present study, the variation trend of biomarkers was observed at four different time-points. Currently, advanced OA can only be alleviated through analgesia or joint replacement, both of which are expensive (23). Therefore, clarifying the pathogenesis as well as the early diagnosis of OA is important for the prevention and treatment of OA. The present study explored the optimal conditions for IL-1β-induced OA in a rat articular chondrocyte cell model. Additionally, the expression of MMPs and subsequent degradation of type II collagen in the course of OA were analyzed. The presented variation trend of the concentration of molecular markers provides a theoretical basis for the diagnosis and screening of OA molecular markers.

Materials and methods

Chondrocyte isolation and culture

Chondrocytes were isolated from male Sprague-Dawley (SD) rats aged 14-24 days, weight 30-50 g. SD rats were bought from thr Animal Experimental Base of Heilongjiang University of Traditional Chinese Medicine. All the animals were kept separately in the animal room. The room was well ventilated, clean and comfortable: The temperature was 21±3˚C, the humidity was 50±15%, the light time was 12 h per day, the food and water supply was sufficient, and the bedding material was changed regularly. The use of rats in the present study was approved by the Laboratory Animal Welfare and Ethics Committee of Northeast Agricultural University (Harbin, China). Chondrocytes from different rats were pooled. Animals were euthanized by placing in a clean, fluoroscopically closed box and CO2 was perfused at a rate of 10-30% of the replacement volume/min into the box. Animal sacrifice was ascertained when the animal was motionless, not breathing, and the pupils became dilated; then CO2 was turned off. The animals were observed for an additional 2 min to confirm sacrifice. In a sterile environment, chondrocytes were isolated from articular cartilage and digested with 0.25% trypsin (Gibco; Thermo Fisher Scientific, Inc.) for 30 min at 37˚C. Subsequently, DMEM/F12 containing 10% FBS (Corning, Inc.) and penicillin-streptomycin (Corning, Inc.) containing 0.2% collagenase type II (Biofroxx) were mixed for 4 h at 37˚C in a shaker to isolate chondrocytes. The cell suspension was centrifuged (400 x g; 7 min) to harvest primary chondrocytes at room temperature. Primary chondrocytes were cultured in DMEM/F12 at 37˚C with 5% CO2 in growth medium. The medium was changed at 24-h intervals. When the cells reached 80% confluence, they were passaged, and the chondrocytes of passage 2 were used for all subsequent experiments.

Cell model

Passage 2 cells were washed three times with serum-starved medium (0.5% FBS) and incubated with DMEM/F12 for 12 h at 37˚C. Chondrocytes were treated with IL-1β (10 ng/ml) (PeproTech, Inc.) for 0, 12, 24 and 48 h at 37˚C. OA is a pathologic process with varying degrees of severity (24). Chondrocytes treated with IL-1β at different time-points were used to simulate an in vitro model of OA. The variation trend of biomarkers at different time-points was observed with the development of OA (14).

Toluidine blue staining

Chondrocytes were washed three times in phosphate-buffered saline (PBS) and fixed with 10% buffered formalin for 30 h at 4˚C. After washing for 5 min with distilled water, chondrocytes were gently washed for 15 min under running water, and then evenly dyed with 1% toluidine blue dye (Gibco; Thermo Fisher Scientific, Inc.) for 2 h at room temperature Finally, the samples were washed with distilled water and examined under a laser confocal optical microscope.

ELISA

According to the manufacturer's instructions, the concentrations of PIICP (cat. no. 88-1052), C2C (cat. no. EHJ-96082r), and CTX-II (cat. no. EHJ-96093r) were measured by ELISA kits (Xiamen Huijia Biological Technology Co., Ltd.). The expression of NO was measured by NO assay kit (cat. no. A013-2; NanJing JianCheng Bioengineering Institute). All assays were repeated three times. All kits are were operated according to the manufacturers' instructions.

Western blot analysis

The protein concentrations were determined using the bicinchoninic acid assay. Cells were rinsed with ice-cold PBS and harvested in lysis buffer (Beyotime Institute of Biotechnology) to obtain total cellular protein, nuclear, or cytoplasmic fractions. Equal quantities (30 µg/lane) of proteins were subjected to 8-12% SDS-PAGE (Beyotime Institute of Biotechnology) and transferred to nitrocellulose filter (NC) membranes (Pall Corporation). Then, the membranes were blocked in PBS containing 20% Tween-20 (PBST; Beyotime Biotechnology, Shanghai, China) plus 5% non-fat dry milk for 1 h at room temperature, and were incubated with primary antibodies overnight at 4˚C. The membranes were washed three times in Tris-buffered saline (TBS) with 20% Tween-20. The blots were then incubated with the secondary antibody conjugated with horseradish peroxidase for 1 h at room temperature. Finally, the western blots were developed using ECL reagent (Beyotime Institute of Biotechnology) through a western blotting detection system.

Primary antibodies included mouse anti-GAPDH (1:3,000, cat. no. TA-08; ZSGB-BIO; OriGene Technologies, Inc.), mouse anti-MMP-13 (1:1,000; cat. no. NB100-91878V; Novus Biologicals, Inc.), rabbit anti-MMP-3 (1:1,000; cat. no. 69926), NF-κB p65 (1:1,000; cat. no. 8242), phospho-NF-κB p65 (1:1,000, cat. no. 3033) (all from Cell Signalling Technology, Inc.) and polyclonal antibody rabbit anti-iNOS (1:500; cat. no. NB300-605AF405; Novus Biologicals, Inc.). Secondary antibodies included goat anti-rabbit-IgG and goat anti-mouse-IgG (1:1,000; cat. no. ZB2305/ZB-2301, ZSGB-BIO; OriGene Technologies, Inc.).

Statistical analysis

All experimental data was analysed using SPSS software (version 19.0 for Windows; SPSS, Inc.). Values are expressed as the mean ± standard deviation (SD). Statistical comparisons between multiple groups were conducted by one-way analysis of variance (ANOVA), followed by Tukey's post hoc test. P<0.05 was considered to indicate a statistically significant difference.

Results

Results of chondrocytes

When the chondrocytes cover 80% of the culture bottle, primary cells can be sub-cultured. After more than three generations, the cells undergo a process known as ‘dedifferentiation’ (25). In the present study, undifferentiated second-generation chondrocytes were used and the cell morphology is shown in Fig. 1.

Results of toluidine blue staining

After dyeing, proteoglycans and the nucleus separated in chondrocytes, where proteoglycans were blue-purple and the nucleus was mazarine. Fig. 2 clearly revealed that the cultured cells were chondrocytes.

Effect of the expression levels of MMP-3 and MMP-13 in IL-1β-induced chondrocytes

The expression levels of MMP-3 and MMP-13 are presented in Fig. 3. The expression levels of MMP-3 increased in a time-dependent manner in IL-1β-induced chondrocytes at 12, 24 and 48 h. MMP-13 expression levels were significantly increased at 12, 24 and 48 h, and were highest at 24 h.

Effect of iNOS and NO expression in IL-1β-induced chondrocytes

Western blot results for the expression level of iNOS are presented in Fig. 4. After IL-1β stimulation, the iNOS expression levels at 12, 24 and 48 h were significantly increased compared to those at 0 h, and reached the maximum value at 24 h (Fig. 4A). As revealed in Fig. 4B, the NO levels differed in culture supernatants at 12, 24, and 48 h compared with the 0-h time-point. In addition, the level of NO was significantly increased at 12, 24 and 48 h, and reached the maximum value at 24 h.

Effects of p65 on the nucleus translocation in IL-1β-induced chondrocytes

Western blot results of the expression levels of p65 and phosphorylated (p)-p65 after chondrocyte stimulation with IL-1β at 0, 30, 60 and 90 min in both the cytoplasm and nucleus are presented in Figs. 5 and 6. Firstly, cytoplasmic extracts exhibited a significantly reduced level of p65 upon IL-1β stimulation. However, the cytoplasmic extracts exhibited the opposite result for p-p65. Secondly, the levels of p65 and p-p65 in chondrocyte nuclei after IL-1β stimulation for 30, 60 and 90 min were increased compared to the group without stimulation (0 min). p65 levels first increased at 30 min and then decreased at 60 and 90 min. p-p65 levels increased and reached the maximum value at 60 min.

IL-1β-induced chondrocyte effect on the levels of CTX-II, C2C and PIICP

ELISA assays revealed that the levels of CTX-II and C2C were significantly increased in IL-1β-induced culture supernatants, and reached a maximum value at 48 h (Fig. 7). However, no significant change was observed in the levels of PIICP after IL-1β treatment.

Discussion

Biomarkers are a class of highly sensitive molecules, and have been extensively studied in OA (9). It is important to study the mechanisms and molecular biomarkers of OA cartilage. Articular cartilage can be damaged by abnormal wear or pathological processes. At the early stage of OA, the ECM changes and the cartilage surface remains intact (25). This change leads to the expression of markers such as Runx2, ColX, and MMP-13(26). As OA further develops, the composition and structure of articular cartilage changes, the proteoglycan and collagen networks break down, the cartilage degrades, and the integrity of the cartilage is lost (27,28). The chondrocytes undergo apoptosis and eventually, the articular cartilage disappears (29). Part of the cartilage forms osteophytes (30). IL-1β (10 ng/ml) (14) has been revealed as an important pro-inflammatory compound that plays key roles in numerous inflammatory responses (31). The development of OA is accompanied by an inflammatory response (32). Therefore, IL-1β, as a pro-inflammatory agent, initiates the activation of inflammation and induces OA. It can be confirmed that articular cartilage is destroyed in OA development (12). In a study by De Visser et al articular cartilage damage was induced on femoral condyles and it was revealed that Fib3-3 was upregulated and may be a biomarker and related to joint degenerative changes (33). In addition, it was revealed by observing different biomarkers in an in vitro OA rat model induced with IL-1α (1 ng/ml) that membrane-free stem cell components (MFSCC) had an effect on cartilage regeneration (34). In these experiments, biomarkers were assessed at specific time-points and did not exhibit trends. In the present study model, rat-specific chondrocytes were used, and different time-points were treated with IL-1β, which could reflect the human OA pathological process to some extent. OA progression is more intuitively reflected by observing biomarker changes at different time-points.

The conducted present experiment only diagnosed OA biomarkers at the cellular level. In follow-up research, we will verify this effect in vivo, which will provide a theoretical basis for the early diagnosis and treatment of OA. The present study revealed that the expression levels of MMP-3, MMP-13, and iNOS and the production of NO were upregulated in IL-1β-induced chondrocytes (35,36). In the progression of OA, MMPs (including MMP-3 and MMP-13) are important regulators. MMP-3, as a matrix lysin, can decrease the expression of collagen and proteoglycans and activate other collagenases (37). MMP-13 is a collagenase that regulates matrix degradation and binds to type II collagen in the ECM (7,38). In addition, proteolytic enzymes and MMPs could be stimulated by IL-1β, which are important factors for cartilage destruction (13). The results of a previous study on type II collagen degradation in chondrocytes were consistent with those of the present study (4). Furthermore, the NF-κB signaling pathway activated by IL-1β, and western blot results revealed that p65 and p-p65 levels increased, which also confirmed the inflammatory response of chondrocytes (39). NF-κB is a transcription factor that plays a vital role in the response to cellular stress as a transcriptional regulator (40). Inflammatory cytokines, such as IL-1β, activate NF-κB to regulate the facilitation of OA. Thus, NF-κB is an important molecule that controls both the normal development and the pathological destruction of cartilage (41). NF-κB is a heterodimeric, and p65 is one of its subunits (42). In the present study, IL-1β stimulated the NF-κB signaling pathway; then, p65 was phosphorylated in the cytoplasm and transferred to the nucleus. Therefore, the level of p65 significantly decreased in cytoplasmic extracts. However, the level of p-p65 exhibited the opposite result. In the chondrocyte nucleus, the level of p65 increased first and then decreased, while the level of p-p65 levels increased.

Western blot analyses revealed that the expression of iNOS increased in chondrocytes, and also, the concentration of NO increased in the chondrocyte culture supernatant (43,44). This suggests that activation of the NF-κB pathway leads to the activation of related transcription factors, further leading to an increase in the synthesis of iNOS and NO. However, the increase of NO concentration stimulated the degradation of the cartilage matrix. In summary, in OA, the NF-κB pathway is activated, which induces a cascade response downstream of the pathway, which promotes cartilage damage. In the present study, the in vitro OA model was induced by treating chondrocytes with IL-1β for different periods of time to observe biomarker changes. According to the results, not only was the pathogenesis and early diagnosis of OA clarified, but also the screening of drugs used for the treatment of OA. The goal of the present study was to provide a summary and guide for the application of in vitro biomarkers for the development of drugs for OA. The present study provided insight into the treatment and relief of OA pathological processes.

Acknowledgements

Not applicable.

Funding

Funding: This work was supported by the National Key R&D Program of China (project no. 2017YFD0502200) and the Applied Technology Research and Development Plan of Heilongjiang (grant no. GX18B023).

Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Authors' contributions

XM and LG designed the study. XM, ZZ and RL performed the cell experiments. XM, MS and XJ collected and analyzed data. XM, ZZ, YM, LG and ZW interpreted the data. XM wrote and edited the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The use of rats in the present study was approved by the Laboratory Animal Welfare and Ethics Committee of Northeast Agricultural University (Harbin, China).

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

French HP, Galvin R, Horgan F and Kenny RA: Prevalence and burden of osteoarthritis amongst older people in Ireland: Findings from The Irish LongituDinal study on ageing (TILDA). Osteoarthritis Cartilage. 23(A188)2015.PubMed/NCBI View Article : Google Scholar

2 

Abramson SB and Attur M: Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther. 11(227)2009.PubMed/NCBI View Article : Google Scholar

3 

Scanzello CR and Goldring SR: The role of synovitis in osteoarthritis pathogenesis. Bone. 51:249–257. 2012.PubMed/NCBI View Article : Google Scholar

4 

Momin M, Guoqing L, Yang W and Li C: Protective effects of gemigliptin against type II collagen degradation in human chondrocytes. Biomed Pharmacother. 104:590–954. 2018.PubMed/NCBI View Article : Google Scholar

5 

Haseeb A and Haqqi TM: Immunopathogenesis of osteoarthritis. Clin Immunol. 146:185–196. 2013.PubMed/NCBI View Article : Google Scholar

6 

Muto T, Kokubu T, Mifune Y, Inui A, Harada Y, Yoshifumi Takase F, Kuroda R and Kurosaka M: Temporary inductions of matrix metalloprotease-3 (MMP-3) expression and cell apoptosis are associated with tendon degeneration or rupture after corticosteroid injection. J Orthop Res. 32:1297–1304. 2014.PubMed/NCBI View Article : Google Scholar

7 

Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, Geoghegan KF and Hambor JE: Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest. 97:761–768. 1996.PubMed/NCBI View Article : Google Scholar

8 

Ying X, Chen X, Cheng S, Shen Y, Peng L and Xu HZ: Piperine inhibits IL-β induced expression of inflammatory mediators in human osteoarthritis chondrocyte. Int Immunopharmacol. 17:293–299. 2013.PubMed/NCBI View Article : Google Scholar

9 

Patra D and Sandell L: Evolving biomarkers in osteoarthritis. J Knee Surg. 24:241–249. 2011.PubMed/NCBI View Article : Google Scholar

10 

Sugiyama S, Itokazu M, Suzuki Y and Shimizu K: Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis. Ann Rheum Dis. 62:27–32. 2003.PubMed/NCBI View Article : Google Scholar

11 

Dejica VM, Mort JS, Laverty S, Antoniou J, Zukor DJ, Tanzer M and Poole AR: Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage. Arthritis Res Ther. 14(R113)2012.PubMed/NCBI View Article : Google Scholar

12 

Boeth H, Macmahon A, Poole AR, Buttgereit F, Önnerfjord P, Lorenzo P, Klint C, Pramhed A and Duda GN: Differences in biomarkers of cartilage matrix turnover and their changes over 2 years in adolescent and adult volleyball athletes. J Exp Orthop. 4(7)2017.PubMed/NCBI View Article : Google Scholar

13 

Madzuki IN, Lau SF, Che Ahmad Tantowi NA, Mohd Ishak NI and Mohamed S: Labisia pumila prevented osteoarthritis cartilage degeneration by attenuating joint inflammation and collagen breakdown in postmenopausal rat model. Infammopharmacology. 26:1207–1217. 2018.PubMed/NCBI View Article : Google Scholar

14 

Li Y, Wang J, Song X, Bai H, Ma T, Zhang Z, Li X, Jiang R, Wang G, Fan X, et al: Effects of baicalein on IL-1β-induced inflammation and apoptosis in rat articular chondrocytes. Oncotarget 8:. 8:90781–90795. 2017.PubMed/NCBI View Article : Google Scholar

15 

Liu B, Zhou Y, Chen X and Peng D: IL-1β-mediated NF-κB signaling augments the osteosarcoma cell growth through modulating miR-376c/TGFA axis. Die Pharmazie. 72:419–424. 2017.PubMed/NCBI View Article : Google Scholar

16 

Wu H, Zhang M, Li W, Zhu S and Zhang D: Stachydrine attenuates IL-1β-induced inflammatory response in osteoarthritis chondrocytes through the NF-κB signaling pathway. Chem Biol Interact. 326(109136)2020.PubMed/NCBI View Article : Google Scholar

17 

Liacini A, Sylvester J, Li WQ and Zafarullah M: Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol. 21:251–162. 2002.PubMed/NCBI View Article : Google Scholar

18 

Zheng W, Chen C, Zhang C, Cai L and Chen H: The protective effect of phloretin in osteoarthritis: An in vitro and in vivo study. Food Funct. 9:263–278. 2018.PubMed/NCBI View Article : Google Scholar

19 

Perkins ND: The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer. 12:121–132. 2012.PubMed/NCBI View Article : Google Scholar

20 

Mobasheri A, Bay-Jensen AC, van Spil WE, Larkin J and Levesque MC: Osteoarthritis year in review 2016: Biomarkers (biochemical markers). Osteoarthritis Cartilage. 25:199–208. 2017.PubMed/NCBI View Article : Google Scholar

21 

Zhang L, Ma S, Su H and Cheng J: Isoliquiritigenin inhibits IL-1β-induced production of matrix metalloproteinase in articular chondrocytes. Mol Ther Methods Clin Dev. 9:153–159. 2018.PubMed/NCBI View Article : Google Scholar

22 

Huang X, Pan Q, Mao Z, Zhang R, Ma X, Xi Y and You H: Sinapic acid inhibits the IL-1β-induced inflammation via MAPK downregulation in rat chondrocytes. Inflammation. 41:562–568. 2018.PubMed/NCBI View Article : Google Scholar

23 

Hayashi D, Roemer FW and Guermazi A: Imaging for osteoarthritis. Ann Phys Rehabil Med. 59:161–169. 2016.PubMed/NCBI View Article : Google Scholar

24 

Mobasheri A and Batt M: An update on the pathophysiology of osteoarthritis. Ann Phys Rehabil Med. 59:333–339. 2016.PubMed/NCBI View Article : Google Scholar

25 

Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, Malaise M and de Seny D: Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem Pharmacol. 165:49–65. 2019.PubMed/NCBI View Article : Google Scholar

26 

Li H, Wang D, Yuan Y and Min J: New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 19(248)2017.PubMed/NCBI View Article : Google Scholar

27 

Wu W, Billinghurst RC, Pidoux I, Antoniou J, Zukor D, Tanzer M and Poole AR: Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis Rheum. 46:2087–2094. 2002.PubMed/NCBI View Article : Google Scholar

28 

Hollander AP, Pidoux I, Reiner A, Rorabeck C, Bourne R and Poole AR: Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J Clin Invest. 96:2859–2869. 1995.PubMed/NCBI View Article : Google Scholar

29 

Mehana EE, Khafaga AF and El-Blehi SS: The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review. Life Sci. 234(116786)2019.PubMed/NCBI View Article : Google Scholar

30 

Xia B, Di Chen Zhang J, Hu S, Jin H and Tong P: Osteoarthritis pathogenesis: A review of molecular mechanisms. Calcif Tissue Int. 95:495–505. 2014.PubMed/NCBI View Article : Google Scholar

31 

Zhou K, Hu L, Liao W, Yin D and Rui F: Coptisine prevented IL-β-induced expression of inflammatory mediators in chondrocytes. Inflammation. 39:1558–1565. 2016.PubMed/NCBI View Article : Google Scholar

32 

Berenbaum F: Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 21:16–21. 2013.PubMed/NCBI View Article : Google Scholar

33 

de Visser HM, Sanchez C, Mastbergen SC, Lafeber FPJG, Henrotin YE and Weinans H: Fib3-3 as a biomarker for osteoarthritis in a rat model with metabolic dysregulation. Cartilage. 10:329–334. 2019.PubMed/NCBI View Article : Google Scholar

34 

Lee HJ, Lee SM, Moon YG, Jung YS, Lee JH, Venkatarame Gowda Saralamma V, Kim YS, Pak JE, Lee HJ, Kim GS and Heo JD: Membrane-free stem cell components inhibit interleukin-1α-stimulated inflammation and cartilage degradation in vitro and in vivo: A rat model of osteoarthritis. Int J Mol Sci. 20(4869)2019.PubMed/NCBI View Article : Google Scholar

35 

Vilá S: Inflammation in osteoarthritis. P R Health Sci J. 36:123–129. 2017.PubMed/NCBI

36 

Goldring MB, Otero M, Plumb DA, Dragomir C, Favero M, El Hachem K, Hashimoto K, Roach HI, Olivotto E, Borzì RM and Marcu KB: Roles of inflammatory and anabolic cytokines in cartilage metabolism: Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater. 21:202–220. 2011.PubMed/NCBI View Article : Google Scholar

37 

Zeng JZ, Ma LF, Meng H, Yu HM, Zhang YK and Guo A: Effect of Ginkgo biloba extract on matrix metalloproteinase-3 expression in a rat model of chondrocyte injury. Genet Mol Res. 14:18280–18286. 2015.PubMed/NCBI View Article : Google Scholar

38 

Piecha D, Weik J, Kheil H, Becher G, Timmermann A, Jaworski A, Burger M and Hofmann MW: Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants. Inflamm Res. 59:379–389. 2010.PubMed/NCBI View Article : Google Scholar

39 

Rigoglou S and Papavassiliou AG: The NF-κB signalling pathway in osteoarthritis. Int J Biochem Cell Biol. 45:2580–2584. 2013.PubMed/NCBI View Article : Google Scholar

40 

Jimi E, Fei H and Nakatomi C: NF-κB signaling regulates physiological and pathological chondrogenesis. Int J Mol Sci. 20(6275)2019.PubMed/NCBI View Article : Google Scholar

41 

De Luca F: Role of nuclear factor kappa B (NF-κB) in growth plate chondrogenesis. Pediatr Endocrinol Rev. 13:720–730. 2016.PubMed/NCBI

42 

Robinson SM and Mann DA: Role of nuclear factor kappaB in liver health and disease. Clin Sci (Lond). 118:691–705. 2010.PubMed/NCBI View Article : Google Scholar

43 

Dai W, Liang Z, Liu H, Zhao G and Ju C: Lunasin abrogates the expression of matrix metalloproteinases and reduction of type II collagen. Artif Cells Nanomed Biotechnol. 47:3259–3264. 2019.PubMed/NCBI View Article : Google Scholar

44 

Moqbel SAA, He Y, Xu L, Ma C, Ran J, Xu K and Wu L: Rat chondrocyte inflammation and osteoarthritis are ameliorated by madecassoside. Oxid Med Cell Longev. 2020(7540197)2020.PubMed/NCBI View Article : Google Scholar

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Ma X, Zhang Z, Shen M, Ma Y, Li R, Jin X, Gao L and Wang Z: Changes of type II collagenase biomarkers on IL‑1β‑induced rat articular chondrocytes Corrigendum in /10.3892/etm.2023.12040. Exp Ther Med 21: 582, 2021
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Ma, X., Zhang, Z., Shen, M., Ma, Y., Li, R., Jin, X. ... Wang, Z. (2021). Changes of type II collagenase biomarkers on IL‑1β‑induced rat articular chondrocytes Corrigendum in /10.3892/etm.2023.12040. Experimental and Therapeutic Medicine, 21, 582. https://doi.org/10.3892/etm.2021.10014
MLA
Ma, X., Zhang, Z., Shen, M., Ma, Y., Li, R., Jin, X., Gao, L., Wang, Z."Changes of type II collagenase biomarkers on IL‑1β‑induced rat articular chondrocytes Corrigendum in /10.3892/etm.2023.12040". Experimental and Therapeutic Medicine 21.6 (2021): 582.
Chicago
Ma, X., Zhang, Z., Shen, M., Ma, Y., Li, R., Jin, X., Gao, L., Wang, Z."Changes of type II collagenase biomarkers on IL‑1β‑induced rat articular chondrocytes Corrigendum in /10.3892/etm.2023.12040". Experimental and Therapeutic Medicine 21, no. 6 (2021): 582. https://doi.org/10.3892/etm.2021.10014