Injectable Hyaluronic-acid-doxycycline Hydrogel Therapy in Experimental Rabbit Osteoarthritis

Overview

Journal BMC Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2013 Apr 12

PMID 23574696

Citations 17

Authors

Hsien-Tsung Lu

Ming-Thau Sheu

Yung-Feng Lin

Jai Lan

Yi-Ping Chin

Ming-Shium Hsieh

Chao-Wen Cheng

Chien-Ho Chen

Affiliations

Soon will be listed here.

Abstract

Background: Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model.

Results: Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity.

Conclusion: Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy.

Citing Articles

Therapeutic Controlled Release Strategies for Human Osteoarthritis.

Wang D, Liu W, Venkatesan J, Madry H, Cucchiarini M Adv Healthc Mater. 2024; 14(2):e2402737.

PMID: 39506433 PMC: 11730424. DOI: 10.1002/adhm.202402737.

Formulation and Comprehensive Evaluation of Biohybrid Hydrogel Membranes Containing Doxycycline or Silver Nanoparticles.

Stan D, Ruta L, Bocancia-Mateescu L, Mirica A, Stan D, Micutz M Pharmaceutics. 2023; 15(12).

PMID: 38140037 PMC: 10747233. DOI: 10.3390/pharmaceutics15122696.

Review of Intra-Articular Use of Antibiotics and Antiseptic Irrigation and Their Systematic Association with Chondrolysis.

Post H, Blankespoor M, Ierulli V, Morey T, Schroeppel J, Mulcahey M Kans J Med. 2023; 16:272-276.

PMID: 37954883 PMC: 10635690. DOI: 10.17161/kjm.vol16.20357.

Identification and analysis of RNA-5-methylcytosine-related key genes in osteoarthritis.

Yu Y, Lu S, Liu X, Li Y, Xu J BMC Genomics. 2023; 24(1):539.

PMID: 37700248 PMC: 10496305. DOI: 10.1186/s12864-023-09651-4.

The Current Role of Disease-modifying Osteoarthritis Drugs.

Rodriguez-Merchan E Arch Bone Jt Surg. 2023; 11(1):11-22.

PMID: 36793668 PMC: 9903308. DOI: 10.22038/ABJS.2021.56530.2807.

References

Thomas C, Fuller C, Whittles C, Sharif M . Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthritis Cartilage. 2006; 15(1):27-34. DOI: 10.1016/j.joca.2006.06.012. View

Mihara M, Higo S, Uchiyama Y, Tanabe K, Saito K . Different effects of high molecular weight sodium hyaluronate and NSAID on the progression of the cartilage degeneration in rabbit OA model. Osteoarthritis Cartilage. 2006; 15(5):543-9. DOI: 10.1016/j.joca.2006.11.001. View

Attur M, Patel R, Patel P, Abramson S, Amin A . Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide. J Immunol. 1999; 162(6):3160-7. View

Brown T, Laurent U, Fraser J . Turnover of hyaluronan in synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol. 1991; 76(1):125-34. DOI: 10.1113/expphysiol.1991.sp003474. View

Takahashi K, Goomer R, Harwood F, Kubo T, Hirasawa Y, Amiel D . The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage. 1999; 7(2):182-90. DOI: 10.1053/joca.1998.0207. View

Li P, Raitcheva D, Hawes M, Moran N, Yu X, Wang F . Hylan G-F 20 maintains cartilage integrity and decreases osteophyte formation in osteoarthritis through both anabolic and anti-catabolic mechanisms. Osteoarthritis Cartilage. 2012; 20(11):1336-46. DOI: 10.1016/j.joca.2012.07.004. View

Brandt K, Mazzuca S, Katz B, Lane K, Buckwalter K, Yocum D . Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005; 52(7):2015-25. DOI: 10.1002/art.21122. View

Oka H, Akune T, Muraki S, Tanaka S, Kawaguchi H, Nakamura K . The mid-term efficacy of intra-articular hyaluronic acid injections on joint structure: a nested case control study. Mod Rheumatol. 2012; 23(4):722-8. DOI: 10.1007/s10165-012-0725-7. View

Larsen N, Dursema H, Pollak C, Skrabut E . Clearance kinetics of a hylan-based viscosupplement after intra-articular and intravenous administration in animal models. J Biomed Mater Res B Appl Biomater. 2011; 100(2):457-62. DOI: 10.1002/jbm.b.31971. View

10.

Amin A, Attur M, Thakker G, Patel P, Vyas P, Patel R . A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci U S A. 1996; 93(24):14014-9. PMC: 19486. DOI: 10.1073/pnas.93.24.14014. View

11.

Iacob S, Knudson C . Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes. Int J Biochem Cell Biol. 2005; 38(1):123-33. PMC: 3139231. DOI: 10.1016/j.biocel.2005.08.011. View

12.

Borderie D, Hernvann A, Hilliquin P, Lemarchal H, Kahan A, Ekindjian O . Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells. Inflamm Res. 2001; 50(8):409-14. DOI: 10.1007/PL00000263. View

13.

Brandt K, Mazzuca S . Experience with a placebo-controlled randomized clinical trial of a disease-modifying drug for osteoarthritis: the doxycycline trial. Rheum Dis Clin North Am. 2006; 32(1):217-34, xi-xii. DOI: 10.1016/j.rdc.2005.11.002. View

14.

Nganvongpanit K, Pothacharoen P, Suwankong N, Ong-Chai S, Kongtawelert P . The effect of doxycycline on canine hip osteoarthritis: design of a 6-months clinical trial. J Vet Sci. 2009; 10(3):239-47. PMC: 2801128. DOI: 10.4142/jvs.2009.10.3.239. View

15.

Kawano T, Miura H, Mawatari T, Moro-oka T, Nakanishi Y, Higaki H . Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis. Arthritis Rheum. 2003; 48(7):1923-9. DOI: 10.1002/art.11172. View

16.

Amin A, Patel R, Thakker G, Lowenstein C, Attur M, Abramson S . Post-transcriptional regulation of inducible nitric oxide synthase mRNA in murine macrophages by doxycycline and chemically modified tetracyclines. FEBS Lett. 1997; 410(2-3):259-64. DOI: 10.1016/s0014-5793(97)00605-4. View

17.

Pardy C, Matyas J, Zernicke R . Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury. J Appl Physiol (1985). 2004; 97(4):1254-60. DOI: 10.1152/japplphysiol.00122.2004. View

18.

Vincent H, Montero C, Conrad B, Horodyski M, Connelly J, Martenson M . "Functional pain," functional outcomes, and quality of life after hyaluronic acid intra-articular injection for knee osteoarthritis. PM R. 2013; 5(4):310-8. DOI: 10.1016/j.pmrj.2013.01.004. View

19.

Hogenmiller M, Lozada C . An update on osteoarthritis therapeutics. Curr Opin Rheumatol. 2006; 18(3):256-60. DOI: 10.1097/01.bor.0000218945.96988.0a. View

20.

Pelletier J . Rationale for the use of structure-modifying drugs and agents in the treatment of osteoarthritis. Osteoarthritis Cartilage. 2003; 12 Suppl A:S63-8. DOI: 10.1016/j.joca.2003.09.014. View