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Ex vivo model exhibits protective effects of sesamin against destruction of cartilage induced with a combination of tumor necrosis factor-alpha and oncostatin M.

Khansai M, Boonmaleerat K, Pothacharoen P, Phitak T, Kongtawelert P - BMC Complement Altern Med (2016)

Bottom Line: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis.Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA.

View Article: PubMed Central - PubMed

Affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

ABSTRACT

Background: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-α and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-α and/or OSM in order to investigate the effects of sesamin on TNF-α and OSM in the cartilage degradation model.

Methods: A porcine cartilage explant was induced with a combination of TNF-α and OSM (test group) or IL-1β and OSM (control group) followed by a co-treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator.

Results: The combination of TNF-α and OSM promoted cartilage degradation more than either TNF-α or OSM alone and was comparable with the combination of IL-1β and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.

Conclusions: Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-α and OSM as well.

No MeSH data available.


Related in: MedlinePlus

Significant S-GAGs depletion and uronic acid remaining in cartilage when induced with TNF-α/OSM alone or TNF-α in combination with OSM. The levels of S-GAGs released in the media were assayed as described in the Methods section. a S-GAGs released in the media represented as the percentage of accumulation of S-GAGs that were released at 7 days and 14 days. b Percentage of uronic acid retained in the cartilage after treatment ended (14 days). Values are presented as mean ± SD (n = 3). * = p < 0.05; ** = p < 0.01 versus normal control. Data represents 3 separate cartilage samples
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Fig1: Significant S-GAGs depletion and uronic acid remaining in cartilage when induced with TNF-α/OSM alone or TNF-α in combination with OSM. The levels of S-GAGs released in the media were assayed as described in the Methods section. a S-GAGs released in the media represented as the percentage of accumulation of S-GAGs that were released at 7 days and 14 days. b Percentage of uronic acid retained in the cartilage after treatment ended (14 days). Values are presented as mean ± SD (n = 3). * = p < 0.05; ** = p < 0.01 versus normal control. Data represents 3 separate cartilage samples

Mentions: To assess the strength of pro-inflammatory cytokines on cartilage degradation, the explants were stimulated with TNF-α or OSM alone or a combination of TNF-α and OSM at concentrations of 6.25, 12.5, and 25 ng/ml for 14 days. The cultured media were collected every 7 days and replaced with the same conditional treatment. After the experiment ended, the explants were harvested. The cultured media that were collected on day 7 and day 14 of the culture were inspected to determine S-GAGs levels, while the explants were checked for remaining amounts of uronic acid. After the 14-day period, it was shown that the presence of TNF-α or OSM alone in the porcine cartilage explant culture induced a low level of proteoglycan depletion in a dose-dependent manner (Fig. 1). TNF-α or OSM alone at 25 ng/ml induced S-GAGs release at about 113 and 115 % when normalized with the control (control = 100 %), respectively (Fig.1a). However, a combination of both cytokines increased S-GAGs release to about 134 % (Fig. 1a). Moreover, it was shown in the levels of remaining uronic acid that OSM had a synergistic effect with TNF-α (Fig. 1b). The combination of 25 ng/ml TNF-α and OSM exhibited the highest level of the cartilage degradation marker. This concentration was chosen selected for use in further experiments.Fig. 1


Ex vivo model exhibits protective effects of sesamin against destruction of cartilage induced with a combination of tumor necrosis factor-alpha and oncostatin M.

Khansai M, Boonmaleerat K, Pothacharoen P, Phitak T, Kongtawelert P - BMC Complement Altern Med (2016)

Significant S-GAGs depletion and uronic acid remaining in cartilage when induced with TNF-α/OSM alone or TNF-α in combination with OSM. The levels of S-GAGs released in the media were assayed as described in the Methods section. a S-GAGs released in the media represented as the percentage of accumulation of S-GAGs that were released at 7 days and 14 days. b Percentage of uronic acid retained in the cartilage after treatment ended (14 days). Values are presented as mean ± SD (n = 3). * = p < 0.05; ** = p < 0.01 versus normal control. Data represents 3 separate cartilage samples
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940911&req=5

Fig1: Significant S-GAGs depletion and uronic acid remaining in cartilage when induced with TNF-α/OSM alone or TNF-α in combination with OSM. The levels of S-GAGs released in the media were assayed as described in the Methods section. a S-GAGs released in the media represented as the percentage of accumulation of S-GAGs that were released at 7 days and 14 days. b Percentage of uronic acid retained in the cartilage after treatment ended (14 days). Values are presented as mean ± SD (n = 3). * = p < 0.05; ** = p < 0.01 versus normal control. Data represents 3 separate cartilage samples
Mentions: To assess the strength of pro-inflammatory cytokines on cartilage degradation, the explants were stimulated with TNF-α or OSM alone or a combination of TNF-α and OSM at concentrations of 6.25, 12.5, and 25 ng/ml for 14 days. The cultured media were collected every 7 days and replaced with the same conditional treatment. After the experiment ended, the explants were harvested. The cultured media that were collected on day 7 and day 14 of the culture were inspected to determine S-GAGs levels, while the explants were checked for remaining amounts of uronic acid. After the 14-day period, it was shown that the presence of TNF-α or OSM alone in the porcine cartilage explant culture induced a low level of proteoglycan depletion in a dose-dependent manner (Fig. 1). TNF-α or OSM alone at 25 ng/ml induced S-GAGs release at about 113 and 115 % when normalized with the control (control = 100 %), respectively (Fig.1a). However, a combination of both cytokines increased S-GAGs release to about 134 % (Fig. 1a). Moreover, it was shown in the levels of remaining uronic acid that OSM had a synergistic effect with TNF-α (Fig. 1b). The combination of 25 ng/ml TNF-α and OSM exhibited the highest level of the cartilage degradation marker. This concentration was chosen selected for use in further experiments.Fig. 1

Bottom Line: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis.Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA.

View Article: PubMed Central - PubMed

Affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

ABSTRACT

Background: Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-α and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-α and/or OSM in order to investigate the effects of sesamin on TNF-α and OSM in the cartilage degradation model.

Methods: A porcine cartilage explant was induced with a combination of TNF-α and OSM (test group) or IL-1β and OSM (control group) followed by a co-treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator.

Results: The combination of TNF-α and OSM promoted cartilage degradation more than either TNF-α or OSM alone and was comparable with the combination of IL-1β and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.

Conclusions: Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-α and OSM as well.

No MeSH data available.


Related in: MedlinePlus