Potential effect of hyaluronic acid and triamcinolone acetate, alone or combined, on chondrogenic differentiation of mesenchymal stem cells


  • Pablo E. Ocampo São Paulo State University
  • Viviana Vallejo São Paulo State University
  • Luis M. Montoya National University of Colombia
  • Noeme S. Rocha São Paulo State University
  • Fernanda da C. Landim São Paulo State University
  • Sheila C. Rahal São Paulo State University




cell differentiation, cartilage, chondrocytes, chondrogenesis, chondrogenic differentiation, collagen, corticosteroids, glucocorticoid, histology, hyaluronic acid, mesenchymal stem cell, osteoarthritis, triancinolone acetonide, viscosupplementation


Background: Osteoarthritis is a complex degenerative disease with several factors contributing to joint damage. Objective: To compare the potential effect of hyaluronic acid (HA) and triamcinolone acetonide (TA), alone or combined, on the in vitro chondrogenic differentiation process of mesenchymal stem cells (MSCs). Methods: MSCs were divided into four groups: Control, HA, TA, and HA/TA combined. Each treatment group was cultured for 14 days in chondrogenic differentiation medium. The chondrogenic differentiation potential was assessed by histology and immunohistochemistry. Results: The HA and HA/TA-treated MSCs presented histological characteristics similar to native chondrocytes. The extracellular matrix (ECM) of TA-treated MSCs was compact and organized. Glycosaminoglycan staining was intense in Control, moderate in TA, slight in HA/TA, and undetectable in HA. Type II collagen immunoreactivity was high in the TA-treated ECM and MSCs. Conclusions: Histological analysis shows that HA influences morphological development similar to chondrocytes of the MSCs, but with low expression of specific cartilage molecules. The TA promotes formation of a compact and organized ECM.

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Author Biographies

Pablo E. Ocampo, São Paulo State University

São Paulo State University (Unesp), School of Veterinary Medicine and Animal Science, Botucatu.

Viviana Vallejo, São Paulo State University

São Paulo State University (Unesp), School of Veterinary Medicine and Animal Science, Botucatu.

Luis M. Montoya, National University of Colombia

Faculty of Veterinary Medicine, National University of Colombia, Bogotá, Colombia. Research Group in Veterinary Pathology.

Noeme S. Rocha, São Paulo State University

São Paulo State University (Unesp), School of Veterinary Medicine and Animal Science, Botucatu.

Fernanda da C. Landim, São Paulo State University

São Paulo State University (Unesp), School of Veterinary Medicine and Animal Science, Botucatu.

Sheila C. Rahal, São Paulo State University

São Paulo State University (Unesp), School of Veterinary Medicine and Animal Science, Botucatu.


Amaral AS. Tumor venéreo transmissível canino: critérios citológicos de malignidade e caracterizacao citomorfológica correlacionada a imunocitoquímica e lesoes de DNA. Tese de Doutorado em Medicina Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, Botucatu. 228p. 2005. URL: http://hdl.handle.net/11449/101297

Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak, F. Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 2004; 25(16):3211-3222. DOI: https://doi.org/10.1016/i.biomaterials.2003.10.045

Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 2004; 8(3):301-316. DOI: https://doi.org/10.1111/i.1582-4934.2004.tb00320.x

Bhumiratana S, Eton RE, Oungoulian SR, Wan LQ, Ateshian GA, Vuniak-Novakovic G. Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation. Proc Natl Acad Sci USA 2014; 111(19):6940-6945. DOI: https://doi.org/10.1073/pnas.1324050111

Bowman S, Awad ME, Hamrick MW, Hunter M, Fulzele S. Recent advances in hyaluronic acid basedtherapy for osteoarthritis. CTM 2018;7(1):6. DOI: https://doi.org/10.1186/s40169-017-0180-3

Céleste C, Ionescu M, Poole AR, Laverty S. Repeated intraarticular iniections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid. J Orthop Res 2005; 23(3):602-610. DOI: https://doi.org/10.1016/i.orthres.2004.10.003

Chung J, Song M, Ha CW, Kim JA, Lee CH, Park YB. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther 2014; 5(2):39. DOI: https://doi.org/10.1186/scrt427

Florine EM, Miller RE, Porter RM, Evans CH, KurzB, GrodzinskyAJ. Effects of dexamethasone on mesenchymal stromal cell chondrogenesis and aggrecanase activity: comparison of agarose and self-assembling peptide scaffolds. Cartilage 2013; 4(1):63-74. DOI: https://dx.doi.org/10.1177%2F1947603512455196

Fox SM. Chronic pain in small animal medicine. London: Manson Pub; 2010.

Freshney RI. Culture of animal cells: A manual of basic technique and specialized applications. New Jersey: John Wiley & Sons; 2010. DOI: https://doi.org/10.1002/9780470649367

Goldberg VM, Goldberg L. Intra-articular hyaluronans: the treatment of knee pain in osteoarthritis. J Pain Res 2010; 3:51-56. DOI: https://doi.org/10.2147/ipr.s4733

Golding D, Brock J, Whiting B, Lee PYF. Intra-articular iniections for management of knee osteoarthritis. J Arthritis 2017; 6(3):1-4. DOI: https://doi.org/10.4172/2167-7921.1000242

Goldring MB. Articular cartilage degradation in osteoarthritis. HSS J 2012; 8(1):7-9. DOI: https://doi.org/10.1007/s11420-011-9250-z

Goodrich LR, Nixon JN. Medical treatment of osteoarthritis in the horse - a review. Vet J 2006; 171(1): 51-69. DOI: https://doi.org/10.1016/i.tvil.2004.07.008

Grodzinsky AJ, Wang Y, Kakar S, Vrahas MS, Evans CH. IntraDarticular dexamethasone to inhibit the development of postDtraumatic osteoarthritis. J Orthop Res 2017; 35(3):406-411. DOI: https://doi.org/10.1002/ior.23295

Hart LE. In knee OA, intraarticular triamcinolone increased cartilage loss and did not differ from saline for knee pain. Ann Intern Med. 2017; 167:JC27. DOI: https://doi.org/10.7326/ACPJC-2017-167-6-027

Hepper CT, Halvorson JJ, Duncan ST, Gregory AJ, Dunn WR, Spindler KP. The efficacy and duration of intra-articular corticosteroid iniection for knee osteoarthritis: a systematic review of level I studies. J Am Acad Orthop Surg 2009; 17(10):638-646. DOI: https://doi:10.5435/00124635-200910000-00006

Jakobsen RB, 0strup E, Zhang X, Mikkelsen TS, Brinchmann JE. Analysis of the effects of five factors relevant to in vitro chondrogenesis of human mesenchymal stem cells using factorial design and high throughput mRNA-profiling. PLoS One 2014; 9(5):e96615. DOI: https://doi.org/10.1371/iournal.pone.0096615

Jansen I, Tellegen A, Tryfonidou M, Óner C, Saris D, Woike N, Creemers L. Brief exposure to triamcinolone acetonide, but not its continous presence, strongly inhibits cartilage regeneration by chondrocytes. Osteoarthritis Cartilage 2016; 24:S337. DOI: https://doi.org/10.1016/i._ioca.2016.01.606

Jo CH, Lee YG, Shin WH, Kim H, Chai, JW, Jeong EC, Kim J, Shim H, Shin I, Ra JC, Oh S, Yoon K. Intra-articular iniection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proofDofDconcept clinical trial. Stem Cells 2014; 32(5):1254-1266. DOI: https://doi.org/10.1002/stem.1634

Larson CM, Kelley SS, Blackwood AD, Banes AJ, Lee GM. Retention of the native chondrocyte pericellular matrix results in significantly improved matrix production. Matrix Biol 2002; 21(4):349-359. DOI: https://doi.org/10.1016/S0945-053X(02)00026-4

Legré-Boyer V. Viscosupplementation: techniques, indications, results. Orthop Traumatol Surg Res 2015; 101(1):S101-S108. DOI: https://doi.org/10.1016/i.otsr.2014.07.027

Levett PA, Melchels FP, Schrobback K, Hutmacher DW, Malda J, Klein TJ. A Biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate. Acta Biomater 2014; 10(1):214-223. DOI: https://doi.org/10.1016/i.actbio.2013.10.005

Lo GH, LaValley M, McAlindon T, Felson DT. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. J Am Med Assoc 2003; 290(23):3115-3121. DOI: https://doi.org/10.1001/iama.290.23.3115

Lovati AB, Corradetti B, Consiglio AL, Recordati C, Bonacina E, Bizzaro D, Cremonesi F. Comparison of equine bone marrow, umbilical cord matrix and amniotic fluid-derived progenitor cells. Vet Res Commun 2011; 35(2):103-121. DOI: https://doi.org/10.1007/s11259-010-9457-3

Maieed MH, Sherazi SAA, Bacon D, Baiwa ZH. Pharmacological treatment of pain in osteoarthritis: a descriptive review. Curr Rheumatol Rep 2018; 20(12). DOI: https://doi.org/10.1007/s11926-018-0794-5

Mak J, Jablonski CL, Leonard CA, Dunn JF, Rahario E, Matyas JR, Biernaskie J, Krawetz RJ. Intra-articular iniection ofsynovial mesenchymal stem cells improves cartilage repair in a mouse iniury model. Sci Rep 2016; 6:23076. DOI: https://doi.org/10.1038/srep23076

March L, Cross M, Lo C, Arden N, Gates L, Leyland K, King L. "Osteoarthritis: A serious disease." OARSI.org. 2016. Available at: https://www.oarsi.org/education/oarsi-resources/oarsi-white-paper-oa-serious-disease

Matsiko A, Levingstone TJ, Gleeson JP, O'brien FJ. Incorporation of TGFDBeta 3 within collagen-hyaluronic acid scaffolds improves their chondrogenic potential. Adv Healthc Mater 2015; 4(8):1175-1179. DOI: https://doi.org/10.1002/adhm.201500053

McGeady TA. Quinn PJ, FitzPatrick ES, Ryan MT, Kilroy D, Lonergan P. Veterinary Embryology. Oxford, UK: J.W. & Sons. 2017.

McIlwraith CW. The use of intra-articular corticosteroids in the horse: what is known on a scientific basis? Equine Vet J 2010; 42(6):563-571. DOI: https://doi.org/10.1111/i.2042-3306.2010.00095.x

McIlwraith CW, Frisbie DD, Kawcak CE. The Horse as a model of naturally occurring osteoarthritis. Bone Joint Res 2012; 1(11):297-309. DOI: https://doi.org/10.1302/2046-3758.111.2000132

Pekarek B, Osher L, Buck S, Bowen M. Intra-articular corticosteroid iniections: a critical literature review with up-to-date findings. Foot (Edinb) 2011; 21(2):66-70. DOI: https://doi.org/10.1016/i.foot.2010.12.001

Randau TM, Schildberg FA, Alini M, Wimmer MD, Haddouti EM, Gravius S, Stoddart MJ. The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells. PLoS One 2013; 8(8):e72973. DOI: https://doi.org/10.1371/iournal.pone.0072973

Richardson DW, Dodge GR. Dose-dependent effects of corticosteroids on the expression of matrix-related genes in normal and cytokine-treated articular chondrocytes. IR 2003; 52(1):39-49. DOI: https://doi.org/10.1007/s000110300012

Schuurman W. Harimulyo EB, Gawlitta D, Woodfield TB, Dhert WJ, van Weeren PR, Malda J. Three-dimensional assembly of tissue-engineered cartilage constructs results in cartilaginous tissue formation without retainment of zonal characteristics. J Tissue Eng Regen Med 2016; 10(4):315-324. DOI: https://doi.org/10.1002/term.1726

Sekiya I, Vuoristo JT, Larson BL, Prockop DJ. In Vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Proc Natl Acad Sci USA 2002; 99(7):4397-4402. DOI: https://dx.doi.org/10.1073%2Fpnas.052716199

Siengdee P, Radeerom T, Kuanoon S, Euppayo T, Pradit W, Chomdei S, Ongchai S, Nganvongpanit K. Effects of corticosteroids and their combinations with hyaluronanon on the biochemical properties of porcine cartilage explants. BMC Vet Res 2015; DOI: https://dx.doi.org/10.1186%2Fs12917-015-0611-6

Silvinato A, Bernardo WM. Inflammatory arthritis or osteoarthritis of the knee - Efficacy of intra-joint infiltration of methylprednisolone acetate versus triamcinolone acetonide or triamcinolone hexacetonide. Rev Assoc Med Bras 2017; 63(10):827-836. DOI: https://doi.org/10.1590/1806-9282.63.10.827

Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem 2015; 17(1):11-22. DOI: https://doi.org/10.1016/i.stem.2015.06.007

Vaca-González JJ, Gutiérrez ML, Garzón-Alvarado DA. Cartílago articular: estructura, patologías y campos eléctricos como alternativa terapéutica. Revisión de conceptos actuales. Rev Colomb Ortop Traumatol 2017; 31(4):202-210. DOI: https://doi.org/10.1016/i.rccot.2017.06.002

Wang CT, Lin J, Chang CJ, Lin YT, Hou SM. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee: a meta-analysis of randomized controlled trials. J Bone Joint Surg Am 2004; 86(3):538-45. DOI: https://doi.org/10.2106/00004623-200403000-00012

Wernecke C, Braun HJ, Dragoo JL. The effects of intra-articular corticosteroids on articular cartilage. Orthop J Sports Med 2015; 3(5):2325967115581163. DOI: https://doi.org/10.1177/2325967115581163

Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials 2010; 31(4):631-640. DOI: https://doi.org/10.1016/i.biomaterials.2009.09.089

Yang IH, Kim SH, Kim YH, Sun HJ, Kim SJ, Lee JW. Comparison of phenotypic charac-terization between 'alginate bead' and 'pel-let' culture systems as chondrogenic differen-tiation models for human mesencgymal stem cells. Yonsei Med J 2004; 45(5):891-900. DOI: https://doi.org/10.3349/ymi.2004.45.5.891

Zhang Z, McCaffery JM, Spencer RG, Francomano CA. Hyaline Cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants. J Anat 2004; 205(3):229-37. DOI: https://doi.org/10.1111/i.0021-8782.2004.00327.x

Zhu M, Feng Q, Bian L. Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels. Acta biomaterialia 2014; 10(3):1333-1340.DOI: https://doi.org/10.1016/i.actbio.2013.12.015




How to Cite

Ocampo, P. E., Vallejo, V., Montoya, L. M., Rocha, N. S., Landim, F. da C., & Rahal, S. C. (2020). Potential effect of hyaluronic acid and triamcinolone acetate, alone or combined, on chondrogenic differentiation of mesenchymal stem cells. Revista Colombiana De Ciencias Pecuarias, 34(3), 212–223. https://doi.org/10.17533/udea.rccp.v34n3a06



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