Effects of Nonsteroidal Anti-inflammatory Drugs on Chondrogenic Differentiation
Abstract
BACKROUND: NSAIDs represent a large class of drugs used for their analgesic and anti-inflammatory effects. Background Nevertheless, their effects on chondrogenic differentiation are not known. The present study examines the potential effects of five different NSAIDs, namely Etodolac, Dexketoprofen, Acetaminophen (Paracetamol), Lornoxicam and Ibuprofen on cell viability as well as chondrogenic differentiation using a mouse embryonic ATDC5-cell-derived chondrocyte model.
METHODS: ATDC5 cells were treated with different concentrations of the NSAIDs. The viablility was evaluated by MTT assay while q-PCR analyses of gene expression of chondrogenic markers (Aggrecan, SOX-9, COL1 and COL2) on 5th & 10th day. Early glycosaminoglycan changes in articular cartilage were determined by safranin-O staining.
RESULTS: No clinical relevant concentration of Lornoxicam, Dexketoprofen and Ibuprofen proved beneficial influence on cell survival. Dexketoprofen and Lornoxicam promoted chondrogenesis through a significant increase of the Aggrecan and COL2 gene expression(levels) when compared to control samples. Histological staining further revealed that Lornoxicam and Dexketoprofen significantly increased glycosaminoglycan content, suggestive of enhanced chondrogenic differentiation.
CONCLUSION: Of all investigated NSAIDs, lornoxicam performed best in terms of chondrogenic differentiation and appears as the most suited for therapeutic approaches targeting cartilage repair / regeneration. These results are further improved with ITS supplementation, indicating a potential synergistic effect to improve cartilage tissue engineering.
Keywords: NSAIDs, chondrogenic differentiation, Lornoxicam and Dexketoprofen
Keywords:
NSAIDs, chondrogenic differentiation, Lornoxicam, DexketoprofenDOI
https://doi.org/10.22270/jddt.v14i9.6781References
Johnstone B., et al. "In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells." Experimental Cell Research, 1998;238(1):265-272. https://doi.org/10.1006/excr.1997.3858 PMid:9457080
Eren, M., et al. "The influence of nonsteroidal anti-inflammatory drugs on the chondrogenic differentiation of mesenchymal stem cells." Journal of Orthopaedic Research, 2015;33(7):1001-1009.
Chen, F. H., et al. "The effects of non-steroidal anti-inflammatory drugs on human chondrocyte proliferation and extracellular matrix turnover." Journal of Orthopaedic Research, 2009;27(1):134-139. https://doi.org/10.1201/9781910227817-27
Miyazawa, K., et al. "Effects of etodolac, a selective COX-2 inhibitor, on human chondrocyte functions." Biochemical Pharmacology, 2000;59(7):903-910.
Carvalho, A. M., et al. "Dexketoprofen trometamol inhibits prostaglandin synthesis in chondrocytes: Implications for cartilage repair." European Journal of Pharmacology, 799, 26-32.Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther. 2017;2005.
Zhang, R. X., et al. "Acetaminophen and chondrocyte differentiation: Effects and mechanisms." Clinical Orthopaedics and Related Research, 2003;406:246-252. https://doi.org/10.1097/00003086-200301000-00035
Warden SJ. Prophylactic use of NSAIDs by athletes: a risk/benefit assessment. Phys Sportsmed. 2010. https://doi.org/10.3810/psm.2010.04.1770 PMid:20424410
Zhang, F., et al. "Effects of ibuprofen on chondrogenesis of mesenchymal stem cells and cartilage repair." Journal of Orthopaedic Research, 2011;29(6):889-895.
Goldring MB, Tsuchimochi K, Ijiri K. "The control of chondrogenesis." Journal of Cellular Biochemistry, 2006;97(1):33-44. https://doi.org/10.1002/jcb.20652 PMid:16215986
Published



How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).