Efeito precoce do concentrado autólogo de plaquetas sobre a osteoartrose induzida em coelhos: Níveis plasmáticos de PDGF e TGF-β1 e seu potencial como biomarcadores

Resumen

The objective of this study was to determinate the plasmatic concentration of the PDGF and TGF-β1 growth factors in rabbits with induced osteoarthrosis by cranial cruciate ligament rupture nd treated with intra-articular autologous platelet concentrate or Ringer’s lactate solution. Fourteen adult male rabbits with an average body mass of 3.0 kg of the New Zealand breed were divided into two groups (I and II). Blood samples were collected before cranial cruciate ligament rupture (moment 1), at substitution moment of the ligament (moment 2) and two weeks after ligament repair (moment 3) and centrifuged to obtain the plasma. The growth factors concentration was evaluated employing ELISA kits specifics for the specie and for growth factors. In autologous platelet concentrate group rabbits, was observed statistically significant difference (P<0.05) in the PDGF levels in moment 3 when compared to the group that received the intra-articular Ringer’s lactate solution. The plasmatic levels of TGF-β1 showed statistically significant difference (P<0.05) in the controlled group when compared moment 1 with moment 2 and moment 3, however no significant difference was observed when compared with the group receiving the autologous concentrate platelets in any of the evaluated moments. It can be concluded, that the PDGF can be used as evaluation parameter of the early effect of the intraarticular autologous platelet concentrate.

Palabras clave:

Cranial cruciate ligament

degenerative articular process

growth factors

plasma

regenerative therapy

fatores de crescimento

ligamento cruzado cranial

plasma

processo articular degenerativo

terapia regenerativa

Citas

 Anitua, S.; Prado, R.; Sánchez, M. et al. Platelet-rich plasma: preparation and formulation.Operative Technique in Orthopaedic, v.22, p. 25-32. 2012.

 Argüelles, D.; Carmona, J.U.; Pastor, J. et al. Evaluation of single and double centrifugation tube methods for concentrating equine platelets. Research in Veterinary Science, v.81, p.237-245. 2006.

 Baksh, N.; Hannon, C.P.; Murawski, C.D. et al. Platelet-rich plasma in tendon models: a systematic review of basic science literature. Arthroscopy, v. 29, n. 3, p. 596-607. 2013.

 Bauer, D.C.; Hunter, D.J.; Abramson, S.B. et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis and Cartilage, v.14, p.723-727. 2006.

 Behnke, O.; Forer, A. From megakaryocytes to platelets: platelet morphogenesis takes place in the bloodstream. European Journal of Haematology, v.60, p.3-24, 1998.

 Bennett, N.T.; Schultz, G.S. Growth factors and wound healing: Biochemical properties of growth factors and their receptors. American Journal of Surgery, v.165, n.6, p.728- 737. 1993.

 Bonnet, C.S.; Walsh, D.A. Osteoarthritis, angiogenesis, and inflammation. Rheumatology (Oxford), v.44, n. 1, p.7-16. 2005.

 Boswell, S.G.; Cole, B.J.; Sundman, E.A. Platelet-rich plasma: a milieu of bioactive factors.Arthroscopy, v.28, n.3, p.429-439. 2012.

 Broughton II, G.; Janis, J.E.; Attinger, C.E. The basic science of wound healing. Plastic and Reconstructive Surgery, v.117, p.12S-32S, 2006a (Suppl.7).

 Broughton II, G.; Janis, J.E.; Attinger, C.E. Wound Healing: An Overview. Plastic and Reconstructive Surgery, v.117, p.1e-S-32e-S, 2006b (Suppl.7).

 Carmona, J.U.; López, C. Autologous platelet concentrates as a treatment for shoulder injury in a horse. case report. Journal of Equine Veterinary Science, v.31, n.9, p. 506- 510. 2011.

 Carmona, J.U.; López, C.; Giraldo, C.E. Uso de concentrados autólogos de plaquetas como terapia regenerativa de enfermedades crónicas del aparato musculoesquelético equino.Archivo de
Medicina Veterinaria, v.43, n.1, p.1-10. 2011.

 Carrasco, J.; Bonete, D.; Gomar, R. Plasma rico en plaquetas vs. plasma rico em factores de crecimiento. Revista Española de Cirugía Osteoarticular, v.46, n.239, p.127-140. 2009.

 Cheon, H.; Yu, S.J.; Yoo, D.H. et al. Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-b1 in synovial fibroblasts from rheumatoid arthritis and normal individuals. Clinical and Experimental Immunology, v.127, n.3, p.547-552. 2002.

 Civinini, R.; Macera, A.; Nistri, L. et al. The use of autologous blood-derived growth factors in bone regeneration. Clinical Cases Mineral Bone Metabolism, v.8, n.1, p.25- 31, 2011.

 Colburn, W.A.; De Gruttola, V.G.; De Mets, D.L. et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Biomarkers Definitions Working Group. Clinical Pharmacological & Therapeutics, v.69, p. 89-95. 2001

 Ehrenfest, D.M.D.; Rasmusson, L.; Albrektsson, T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (LPRF). Trends in Biotechnology, v. 27, n. 3, p. 158-167. 2008.

 Flores, J.R.; Gallego, M.A.P.; García-Denche, J.T. Plasma rico en plaquetas: fundamentos biológicos y aplicaciones en cirugía maxilofacial y estética facial. Revista Española de Cirugía Oral y Maxilofacial, v. 34, n. 1, p. 8-17. 2012.

 Harrison, P. Platelet function analysis. Blood Reviews, v.19, n.2, p.111-123. 2005.

 Hakimi, M.; Jungbluth, P.; Sager, M. et al. Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. InjuryInternational Journal
of the Care of the Injured, v.41, n.7, p. 717-723. 2010.

 Iacopetti, I.; Perazzi, A.; Ferrari, V. et al. Application of platelet-rich gel to enhance wound healing in the horse: A case report. Journal of Equine Veterinary Science, v.32, n.3, p.123-128. 2012.

 Intini, G. The use of platelet-rich plasma in bone reconstruction therapy. Biomaterials, v.30, n.28, p.4956-4966. 2009.

 Kang, H.J.; Kang, E.S. Ideal concentration of growth factors in rabbit’s flexor tendon culture.Yonsei Medical Journal, v.40, n.1, p.26-29. 1999.

 Kim, J.H; Park, C.; Park, H.M. Curative effect of autologous platelet-rich plasma on a large cutaneous lesion in a dog. Veterinary Dermatology, v.20, n.2, p. 123-126. 2008.

 Kon, E.; Filardo, G.; Di Matteo, B. et al. Platelet-rich plasma in sports medicine: new treatment for tendon and cartilage lesions. Operative Techniques in Orthopaedics, v.22, n.2, p.78-85. 2012.

 Kraus, V.B.; Blanco, F.J.; Englund, M. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis. Osteoarthritis and Cartilage, v.23, p.686-697, 2015.

 Kraus, V.B.; Burnett, B.; Coindreau, J. et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis and Cartilage, v.19, p.515-542, 2011.

 Lagunas, J.G. Plasma rico en plaquetas. Revista Española de Cirugía Oral y Maxilofacial, v.28, n.2, p.89-99. 2006.

 Lawrence, W.; Diegelmann, R. Growth factors in wound healing. Clinics in Dermatology, v.12, n.1, p.157-169. 1994.

 Lee, A.J.; Chung, W.H.; Kim, D.H. et al. Anterior cruciate ligament reconstruction in a rabbit model using canine small intestinal submucosa and autologous platelet-rich plasma. Journal of Surgery Research, v.178, n.1, p.206-215. 2012.

 Lynch, S.E.; Williams, R.C.; Polson, A.M. et al. A combination of platelet derived and insulin-like growth factors enhances periodontal regeneration. Journal of Periodontology, v. 16, n. 8, p. 545-548. 1989.

 Marx, R.E. Platelet-rich plasma: evidence to support its use. Journal of Oral and Maxillofacial Surgery, v. 62, n. 4, p. 489-496. 2004.

 Matsuda, N.; Lin, W.L.; Kumar, N.M. et al. Mitogenic, chemostatic, synthetyc responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. Journal of Periodontology, v.63, n.6, p.515-25. 1992.

 Milano, G.; Sanna-Passino, E.; Deriu, L. et al. The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: an experimental study in a sheep
model. Osteoarthritis and Cartilage, v.18, n.7, p.971-980. 2010.

 Mishra, A.; Woodall, J.; Vieira, M. Treatment of tendon and muscle using platelet-rich plasma. Clinics in Sports Medicine, v.28, n.1, p.113–125. 2009.

 Niu, T.; Rosen, C.J. The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene, v.361, p.38-56. 2005.

 Osorio-Carmona, E.; Rezende, C.M.F. Osteoartrose: aspectos clínicos e novas perspectivas terapêuticas baseadas na terapia regenerativa. Veterinaria y Zootecnia, v.8, n.2, p.49-71. 2014.

 Patel, S.; Dhillon, M.S.; Aggarwal, S. et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: A prospective, double-blind, randomized trial.American Journal of Sports Medicine, v.41, n.2, p.356-364. 2013.

 Petrigliano, F.P.; McAllister, D.R.; Wu, B.M. Tissue engineering for anterior cruciate ligament reconstruction: A review of current strategies. Journal of Arthroscopic Related Surgery, v.22, n.4, p.441-451. 2006.

 Rezende, M.U de.; Campos, G.C de. A osteoartrite é uma doença mecânica ou inflamatória?Revista Brasileira de Ortopedia, v.48, n.6, p.471-474. 2013.

 Riedel, K.; Riedel, F.; Goessler, U.R. et al. TGF-beta antisense therapy increases angiogenic potential in human keratinocytes in vitro. Archives of Medical Research, v.38, n.1, p.45-51. 2007.

 Saito, M.; Takahashi, K.A.; Arai, Y. et al. Intraarticular administration of platelet-rich plasma with biodegradable gelatin hydrogel microspheres prevents osteoarthritis progression in the rabbit knee. Clinical and Experimental Rheumatology, v. 27, n. 2, p. 201-207. 2009.

 Sánchez, M; Azofra, J; Anitua, E. et al. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Medicine and Science in Sports and Exercise, v.35, n.10, p.1648-1652. 2003.

 Schawalder, P.; Gitterle, E. Eigene methoden zur operativen rekonstruktion bei rupturen des vorderen und hinteren kreuzbandes. Kleintierpraxis, v.7, p.323-330, 1989.

 Schwartz, A.; Martinez-Sanchez, G.; Re, L. Growth factors derived from platelet and its applications in regenerative medicine. Potential use of ozone as activator. Revista Española de Ozonoterapia, v.1, n.1, p.54-73. 2011.

 Silva, R.F. Caracterizações celular e ultra-estrutural do concentrado de plaquetas em cães e gatos e avaliação do seu efeito na osteoartrose em cães. Belo Horizonte, Brasil: Universidade Federal de Minas Gerais, 2012. 88f. Tese (Doutorado em ciência animal).

 Silva, R.F.; Rezende, C.M.F; Paes-Leme, F.O. et al. Evaluación del método del tubo para concentrar plaquetas caninas: estudio celular. Archivos de Medicina Veterinaria, v.43, n.1, p.95-98. 2011a.

 Silva, R.F; Rezende, C.M.F; Paes-Leme, F.O. et al. Evaluación del método del tubo para concentrar plaquetas felinas: estudio celular. Archivos de Medicina Veterinaria, v.43, n.2, p.187-190. 2011b.

 Smith, S.E.; Roukis, T.S. Bone and wound healing augmentation with platelet-rich plasma.Clinics in Podiatric Medicine and Surgery, v.26, n.4, p.559-588. 2009.

 Sohn, D.H.; Sokolove, J.; Sharpe, O. et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Research and Therapy, v.14, n.1, p.R7. 2012.

 Textor, J. Autologous biologic treatment for equine musculoskeletal injuries: Plateletrich plasma and IL-1 receptor antagonist protein. Veterinary Clinics of North America. Equine Practice, v.27, n.2, p.275-298. 2011.

 Tiwari, M.; Bhargava, R. Platelet rich plasma therapy: a comparative effective therapy with promising results in plantar fasciitis. Journal of Clinics Orthopaedics and Trauma, v.4, n.1, p.31-35. 2013.

 Vagdatli, E.; Gonari, E.; Lazaridou, E. et al. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia, v.14, n.1, p.28- 32, 2010.

 Virchenko, O.; Aspenberg, P. How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation. Acta Orthopaedica, v.77, n.5, p.806-812. 2006.

 Wasterlain, A.S.; Braun, H.J.; Dragoo, J.L. Contents and formulations of platelet-rich plasma. Operative Technique in Orthopaedics, v.22, n.1, p.33-42. 2012.

 Weibrich, G; Hansen, T; Kleis, W. et al. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone, v.34, n.4, p.665-671. 2004.

 Xie, X.; Wu, H. Zhao, S. et al. The effect of platelet-rich plasma on patterns of gene expression in a dog model of anterior cruciate ligament reconstruction. Journal of Surgery Research, v.180, n.1, p.80-88. 2013a.

 Xie, X.; Zhao, S.; Wu, H. et al. Platelet-rich plasma enhances autograft revascularization and reinnervation in a dog model of anterior cruciate ligament reconstruction. Jounal of Surgery Research, v.183, n.1, p.214-222. 2013b.