Effects of Diclofenac and Celecoxib on Osteoclastogenesis During Alveolar Bone Healing, in Vivo

Overview

Journal Dent Res J (Isfahan)

Specialty Dentistry

Date 2014 Aug 7

PMID 25097646

Citations 2

Authors

Parichehr Ghalayani

Mohsen Minaiyan

Sayyed Mohammad Razavi

Samira Hajisadeghi

Narges Naghsh

Mohammad Shah Abuie

Affiliations

Soon will be listed here.

Abstract

Background: OSTEOCLASTOGENESIS IS COORDINATED BY THE INTERACTION OF MEMBERS OF THE TUMOR NECROSIS FACTOR (TNF) SUPERFAMILY: Receptor activator of nuclear factor-κB ligand (RANKL) and Osteoprotegerin (OPG). The aim of this study was to compare the effect of two different types of non-steroidal anti-inflammatory drugs (NSAIDs) on the RANKL/OPG balance during the healing of the alveolar process.

Materials And Methods: This was an experimental study, carried on 45 male Wistar rats (200 ± 25 g, 8-10 weeks old). After extraction of the right maxillary first molar, 15 rats received 5 mg/kg/day of diclofenac and 15 rats received 15 mg/kg/day of celecoxib and 15 rats received normal saline. The animals were sacrificed 7, 14 and 21 days after tooth extraction. The number of osteoclasts, OPG and RANKL messenger ribonucleic acid expression were determined by tartrate-resistant acid phosphate (TRAP) staining and polymerase chain reaction (PCR) respectively. The data were analyzed by one-way ANOVA followed by Tukey's post-hoc test. Values of P < 0.05 were considered significant.

Results: On days 7, 14 and 21 the ratio of RANKL/OPG in the control group was higher than diclofenac and celecoxib groups. TRAP immunolabeling of the control group was more than diclofenac group on day 7 and was more than celecoxib group on day 14. On day 21, no significant differences were noted among the three studied groups.

Conclusion: Both drugs affect RANKL/OPG gene expression and also osteoclastogenesis in alveolar socket during the experimental period of 21 days.

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References

Katoh H, Hosono K, Ito Y, Suzuki T, Ogawa Y, Kubo H . COX-2 and prostaglandin EP3/EP4 signaling regulate the tumor stromal proangiogenic microenvironment via CXCL12-CXCR4 chemokine systems. Am J Pathol. 2010; 176(3):1469-83. PMC: 2832166. DOI: 10.2353/ajpath.2010.090607. View

Gerstenfeld L, Einhorn T . COX inhibitors and their effects on bone healing. Expert Opin Drug Saf. 2004; 3(2):131-6. DOI: 10.1517/eods.3.2.131.27335. View

Tanaka H, Mine T, Ogasa H, Taguchi T, Liang C . Expression of RANKL/OPG during bone remodeling in vivo. Biochem Biophys Res Commun. 2011; 411(4):690-4. DOI: 10.1016/j.bbrc.2011.07.001. View

Kellinsalmi M, Parikka V, Risteli J, Hentunen T, Leskela H, Lehtonen S . Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro. Eur J Pharmacol. 2007; 572(2-3):102-10. DOI: 10.1016/j.ejphar.2007.06.030. View

Bruzzaniti A, Baron R . Molecular regulation of osteoclast activity. Rev Endocr Metab Disord. 2006; 7(1-2):123-39. DOI: 10.1007/s11154-006-9009-x. View

Lin J, Callon K, Lin C, Bava U, Zheng M, Reid I . Alteration of bone cell function by RANKL and OPG in different in vitro models. Eur J Clin Invest. 2007; 37(5):407-15. DOI: 10.1111/j.1365-2362.2007.01800.x. View

Lacey D, Timms E, Tan H, Kelley M, Dunstan C, Burgess T . Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93(2):165-76. DOI: 10.1016/s0092-8674(00)81569-x. View

Cannon C, Curtis S, FitzGerald G, Krum H, Kaur A, Bolognese J . Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006; 368(9549):1771-81. DOI: 10.1016/S0140-6736(06)69666-9. View

Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T . Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A. 1990; 87(18):7260-4. PMC: 54723. DOI: 10.1073/pnas.87.18.7260. View

10.

Cottrell J, OConnor J . Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing. Pharmaceuticals (Basel). 2016; 3(5):1668-1693. PMC: 4034003. DOI: 10.3390/ph3051668. View

11.

Seidenberg A, An Y . Is there an inhibitory effect of COX-2 inhibitors on bone healing?. Pharmacol Res. 2004; 50(2):151-6. DOI: 10.1016/j.phrs.2003.12.017. View

12.

Yasuda H, Shima N, Nakagawa N, Mochizuki S, Yano K, Fujise N . Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998; 139(3):1329-37. DOI: 10.1210/endo.139.3.5837. View

13.

Burgess T, Qian Y, Kaufman S, Ring B, Van G, Capparelli C . The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol. 1999; 145(3):527-38. PMC: 2185088. DOI: 10.1083/jcb.145.3.527. View

14.

Silverstein F, Faich G, Goldstein J, Simon L, Pincus T, WHELTON A . Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000; 284(10):1247-55. DOI: 10.1001/jama.284.10.1247. View

15.

Mullis B, Copland S, Weinhold P, Miclau T, Lester G, Bos G . Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. Injury. 2006; 37(9):827-37. DOI: 10.1016/j.injury.2005.12.018. View

16.

Manolagas S . Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000; 21(2):115-37. DOI: 10.1210/edrv.21.2.0395. View

17.

Fracon R, Teofilo J, Satin R, Lamano T . Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry. J Oral Sci. 2008; 50(3):247-52. DOI: 10.2334/josnusd.50.247. View

18.

Karakawa A, Fukawa Y, Okazaki M, Takahashi K, Sano T, Amano H . Diclofenac sodium inhibits NFkappaB transcription in osteoclasts. J Dent Res. 2009; 88(11):1042-7. DOI: 10.1177/0022034509346147. View

19.

Taketa T, Sakai A, Tanaka S, Nakai K, Menuki K, Yamane H . Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells. J Bone Miner Metab. 2008; 26(2):143-51. DOI: 10.1007/s00774-007-0808-2. View

20.

Simonet W, Lacey D, Dunstan C, Kelley M, Chang M, Luthy R . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89(2):309-19. DOI: 10.1016/s0092-8674(00)80209-3. View