Highlights
- •Lyophilized equine platelets derived growth factor (LGF) could repair chondoral defect.
- •LGF lowered the pro-inflammatory cytokines; TNF-α and IL-1β.
- •LGF increased the anabolic and angiogenic growth factors; PDGF and TGF-β1.
- •LGF elevated the expression of chondrogenic-related marker genes; Col I and Col II.
- •LGF decreased the immune-expression of NF-κB p65 and MMP2 proteins.
- •LGF improved the histopathological alterations in osteoarthritis.
Abstract
Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet
rich protein growth factor. It has been successfully applied in various fields of
regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal
conditions. Our study aimed to evaluate the efficacy of intraarticularly injected
LGF for the remedy of articular cartilage injury, commonly characterized by progressive
pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical
cartilage defects were generated in both femoral condylar articular surfaces in twenty
rabbits. The left joint of all animals was injected with the adjuvant as a self-control
negative, while the right joint was injected by LGF. Four- and eight-weeks post-surgery,
the femoral condyles were harvested, and assessed grossly, microscopically and immunohistochemically.
Cytokines (TNF-α, IL-1β, PDGF and TGF-β1) contents of the chondral defects were quantified
by ELISA as well as the gene expression of Col I and Col II via RT-qPCR. The LGF treated
defects showed significant higher ICRS (International cartilage repair society) healing
scores of cartilaginous regeneration with a significant higher histological healing
score on using O'Driscoll histological scoring system. Additionally, LGF significantly
lowered the levels of the pro-inflammatory cytokines TNF-α and IL-1β. It also significantly
increased the anabolic and angiogenic growth factors (PDGF and TGF-β1), and significantly
elevated the expression of chondrogenic-related marker genes; Col I and Col II. The
current study reveals that LGF improves chondral healing and thus it can be a superior
nominee as an adjunctive therapy to positively influence regeneration of chondral
defects in osteoarthritic patients.
Keywords
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References
- The basic science of articular cartilage: structure, composition, and function.Sports Health. 2009; 1: 461-468
- Animal Models of Osteochondral Defect for Testing Biomaterials.Biochem Res Int. 2020; 2020: 10-12
- Animal models of osteochondral defect for testing biomaterials.Biochem Res Int. 2020; : 1-12
- Osteoarthritis – an untreatable disease?.Nat Rev Drug Discov. 2005; 4: 331-344
- Age-related histological changes in calcified cartilage and subchondral bone in femoral heads from healthy humans.Bone. 2019; 129115037
- Tissue-engineering strategies to repair chondral and osteochondral tissue in osteoarthritis: use of mesenchymal stem cells.Curr Rheumatol Rep. 2014; 16: 452-468
- An educational review of cartilage repair: precepts & practice–myths & misconceptions–progress & prospects.Osteoarthr Cartil. 2015; 23: 334-350
- Autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs.Vet Surg. 2008; 37: 311-321
- Treatment of articular cartilage defects: focus on tissue engineering.In Vivo (Brooklyn). 2018; 32: 1289-1300
- Tissue engineering of functional articular cartilage: the current status.Cell Tissue Res. 2012; 347: 613-627
- Intra-articular Atelocollagen injection for the treatment of articular cartilage defects in rabbit model.Tissue Eng Regen Med. 2021; 18: 663-670
- Growth factor content in PRP and their applicability in medicine.J Biol Regul Homeost Agents. 2012; 26: 3-22
- The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich fibrin (L-PRF) clot and membrane.Platelets. 2017; 29: 171-184
- Formulation and Storage of platelet-rich plasma homemade product.Biores Open Access. 2012; 1: 115-123
- Evaluation of three methods of platelet-rich plasma for treatment of equine distal limb skin wounds.J Equine Vet Sci. 2019; 72: 1-7
- Effect of lyophilized growth factors (LGF) derived from equine platelets on experimentally induced skin wound healing in mongrel dogs.Int. J. Vet. Sci. 2021; 10: 75-82
- Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells.Cytotherapy. 2014; 16: 170-180
- Use of canine sourced platelet-rich plasma in a feline contaminated cutaneous wound.Can Vet J. 2017; 58: 141-144
- Co-treatment of wounds in rabbit skin with equine platelet-rich plasma and a commercial ointment accelerates healing.Cienc Anim Bras. 2020; 21 (e-): 56274
- Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model.BMC Musculoskelet Disord. 2011; 12: 259-277
- Promoted inhibition of TLR4/miR-155/NFkB p65 signaling by cannabinoid receptor 2 agonist (AM1241), aborts inflammation and progress of hepatic fibrosis induced by thioacetamide.Chem. Biol. Interact. 2021; 336109398
- Bancroft's theory and practice of histological techniques.2nd ed. Churchill Livingstone, New York2012
- The regenerative effect of platelet-rich plasma on healing in large osteochondral defects.Int Orthop. 2010; 34: 589-597
- Oral and topical anti-inflammatory and antipyretic potentialities of araucaria bidiwillii shoot essential oil and its nanoemulsion in relation to chemical composition.Molecules. 2021; 26: 5833
- Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration.Biomaterials. 2012; l33: 7008-7018
- Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.Stem Cell Res Ther. 2013; 4: 67-80
- Platelet rich plasma: a short overview of certain bioactive components.Open Med J. 2016; 11: 242-247
- Is exclusion of leukocytes from platelet-rich plasma (PRP) a better choice for early intervertebral disc regeneration?.Stem Cell Res Ther. 2018; 9: 199-210
- Leukocyte depletion doesn’t affect the invitro healing ability of platelet rich plasma.Exp Ther Med. 2018; 15: 4029-4038
- Optimized preparation method of platelet-concentrated plasma and non-coagulating platelet derived factor concentrates: maximization of platelet concentration and removal of fibrinogen.Tissue Eng Part C Methods. 2012; 18: 176-185
- Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing.Exp Mol Pathol. 2003; 74: 244-255
- The effects of platelet-rich plasma on cartilage: basic science and clinical application.Oper Tech Sports Med. 2011; 3: 154-159
- Platelet-Rich plasma: growth factors and Pro- and Anti-inflammatory properties.J Periodontol. 2007; 78: 661-669
- Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T–comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model.Osteoarthr Cartil. 2012; 20: 1046-1055
- Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage.Osteoarthr Cartil. 2010; 18: 12-23
- Evaluation of low level laser-activated stromal vascular fraction as a single procedure for treatment of experimental chondral defects.Asian J Anim Sci. 2016; 10: 15-28
- Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model.BMC Musculoskelet Disord. 2011; 12: 259-277
- The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.Mediators Inflamm. 2014; 2014: 1-19
- Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis.Arthritis Rheum. 1998; 41: 2165-2174
- Extracellular matrix production in vitro in cartilage tissue engineering.J Transl Med. 2014; 12: 88
- Interleukin-1beta induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro.Pathobiology. 2000; 68: 144-149
- Prospects for treating osteoarthritis: enzyme-protein interactions regulating matrix metalloproteinase activity.Ther Adv Chronic Dis. 2012; 3: 219-229
- Apoptosis in normal and osteoarthritic human articular cartilage.Ann Rheum Dis. 2000; 59: 959-965
- c-Jun Nterminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis.Can J Physiol Pharm. 2014; 92: 132-139
- Reactive oxygen species and superoxide dismutases: role in joint diseases.Joint Bone Spine. 2007; 74: 324-329
- Platelet rich plasma: a milieu of bioactive factors.Arthrosc. 2012; 28: 429-439
- Autologous protein solution inhibits MMP-13 production by IL-1beta and TNFalpha-stimulated human articular chondrocytes.J Orthop Res. 2011; 29: 1320-1326
- Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes.Am J Sports Med. 2011; 39: 2362-2370
- Increases in levels of procollagenase mRNA in human fibroblasts induced by interleukin-1, tumor necrosis factor-alpha, or serum follow c-jun expression and are dependent on new protein synthesis.Proc Assoc Am Physicians. 1989; 102: 195-203
- NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis.Osteoarthr Cartil. 2006; 14: 839-848
- Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor IkappaBalpha reveals that most, but not all, inflammatory and destructivemediators are NF kappa B dependent.Rheumatology (Oxford). 2006; 45: 1201-1209
- NF-kappaBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1beta-induced and TNF-alpha-induced chondrocytes.Osteoarthr Cartil. 2006; 14: 367-376
- Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-kappaB inhibition via HGF.J Cell Physiol. 2010; 225: 757-766
- Hepatic acute phase proteins–regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB dependent signaling.Eur J Cell Biol. 2012; 91: 496-505
- Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.Ann Rheum Dis. 1992; 51: 1219-1222
- Nitric oxide activates metalloprotease enzymes in articular cartilage.Biochem Bioph Res Co. 1995; 206: 15-21
- TGFbeta inhibits IL-1-induced iNOS expression and NO production in immortalized chondrocytes.Inflamm Res. 2005; 54: 420-427
Article info
Publication history
Published online: February 05, 2022
Accepted:
February 3,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.