Recombinant platelet derived growth factor-BB and hyaluronic acid effect in rat osteoarthritis models.
Ontology highlight
ABSTRACT:
SUBMITTER: Setiawan IGNY
PROVIDER: S-EPMC6411620 | biostudies-literature | 2019 May-Jun
REPOSITORIES: biostudies-literature
Publications
Recombinant platelet derived growth factor-BB and hyaluronic acid effect in rat osteoarthritis models.
Setiawan I Gusti Ngurah Yudhi IGNY Suyasa I Ketut IK Astawa Putu P Dusak I Wayan Suryanto IWS Kawiyana I Ketut Siki IKS Aryana I Gusti Ngurah Wien IGNW
Journal of orthopaedics 20190302 3
Osteoarthritis (OA) arises from imbalance of cartilage metabolism between the synthesis and degradation of type II collagen by the chondrocyte. Collagen type II degradation is characterized by increase in the biomarker of C-telopeptide fragment of type II collagen (CTX-II), while the anabolic process of cartilage is characterized by an increase in the biosynthesis of procollagen amino terminal N-propeptide type IIA (PIIANP). Platelet derived growth factor (PDGF) with Hyaluronic Acid (HA) as a po ...[more]
Similar Datasets
Project description:ObjectiveOsteoarthritis is caused by cartilage degeneration arising from cartilage degradation of type II collagen which synthesis also deteriorated. Nowadays, osteoarthritis is still difficult to handle because of the irreversibility and progressivity of the disease. Regenerative therapy offers a great challenge and better result for osteoarthritis treatment. This study aims to prove that the administration of recombinant platelet-derived growth factor-BB (rrPDGF-BB) with hyaluronic acid (HA) can stimulate the higher forms of chondrocyte and lower the YKL-40 levels as a specific marker of cartilage degradation in mouse knee osteoarthritis model.MethodThis was an experimental study, post-test only control group design using white Wistar rats as subjects that were induced by monosodium iodoacetate (MIA) to create osteoarthritis (OA). The treatment group was given treatment group was given rrPDGF-BB and HA, while no such treatment was given to the control group. The chondrocyte cell count was examined with routine histopathology, and YKL-40 levels were calculated by ELISA.ResultStatistical analysis using independent t-test showed that the mean difference in the number of cell counts of chondrocytes was significantly higher than the control group. While the mean difference of YKL-40 level in the treatment group was significantly lower compared to the control group with.ConclusionWe conclude that the administration of rrPDGF-BB and HA in mouse knee joint osteoarthritis model have a regenerative effect on knee joint cartilage characterized by a higher number of chondrocytes and lower YKL-40 levels.
| S-EPMC6978183 | biostudies-literature
Project description:The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet‑derived growth factor‑BB (PDGF‑BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases. [BMB Reports 2023; 56(8): 445-450].
| S-EPMC10471460 | biostudies-literature
Project description:Yeast Pichia pastoris is a widely used system for heterologous protein expression. However, post-translational modifications, especially glycosylation, usually impede pharmaceutical application of recombinant proteins because of unexpected alterations in protein structure and function. The aim of this study was to identify glycosylation sites on recombinant human platelet-derived growth factor-BB (rhPDGF-BB) secreted by P. pastoris, and investigate possible effects of O-linked glycans on PDGF-BB functional activity. PDGF-BB secreted by P. pastoris is very heterogeneous and contains multiple isoforms. We demonstrated that PDGF-BB was O-glycosylated during the secretion process and detected putative O-glycosylation sites using glycosylation staining and immunoblotting. By site-directed mutagenesis and high-resolution LC/MS analysis, we, for the first time, identified two threonine residues at the C-terminus as the major O-glycosylation sites on rhPDGF-BB produced in P. pastoris. Although O-glycosylation resulted in heterogeneous protein expression, the removal of glycosylation sites did not affect rhPDGF-BB mitogenic activity. In addition, the unglycosylated PDGF-BB?Gly mutant exhibited the immunogenicity comparable to that of the wild-type form. Furthermore, antiserum against PDGF-BB?Gly also recognized glycosylated PDGF-BB, indicating that protein immunogenicity was unaltered by glycosylation. These findings elucidate the effect of glycosylation on PDGF-BB structure and biological activity, and can potentially contribute to the design and production of homogeneously expressed unglycosylated or human-type glycosylated PDGF-BB in P. pastoris for pharmaceutical applications.
| S-EPMC4689512 | biostudies-literature
Project description:BackgroundBioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans.MethodHerein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund's adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively.ResultsCombined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology-related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA.ConclusionConclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php .
| S-EPMC10494357 | biostudies-literature
Project description:Background and purposeSo far, there is only limited information about the regulation of the endogenous synthesis of hydrogen sulfide (H(2) S), an important gaseous signalling molecule. This study was done to evaluate the redox-dependent signalling events that regulate the expression of the H(2) S synthesising enzyme cystathionine-γ-lyase (CSE) in rat mesangial cells.Experimental approachThe effects of platelet-derived growth factor (PDGF)-BB and antioxidants on CSE expression and activity in cultured rat renal mesangial cells were assessed. Activity of nuclear factor erythroid-2-related factor-2 (Nrf2) was measured as the binding capacity to a radiolabelled consensus element by electrophoretic mobility shift assay (EMSA). Furthermore, CSE and Nrf2 expression was analysed in a rat model of anti-Thy-1-induced glomerulonephritis by immunohistochemistry.Key resultsTreatment of mesangial cells with PDGF-BB resulted in a marked time- and dose-dependent up-regulation of CSE mRNA and protein levels, as well as CSE activity accompanied with increased formation of reactive oxygen species. Remarkably, co-administration of antioxidants, such as N-acetylcysteine, ebselen or diphenylene iodonium chloride, drastically reduced PDGF-BB-induced CSE expression. PDGF-BB induced binding of Nrf2 to a corresponding consensus antioxidant element in a redox-dependent manner. Furthermore, PDGF-BB-induced CSE expression in mouse mesangial cells was completely abolished in Nrf2 knockout mice compared with wild-type mice. In a rat model of anti-Thy-1-induced proliferative glomerulonephritis, we observed a marked up-regulation of CSE protein paralleled by a stabilization of Nrf2 protein.Conclusions and implicationsPDGF-BB regulated CSE via a redox-mediated activation of Nrf2. Such action would aid the resolution of glomerular inflammatory diseases.Linked articleThis article is commented on by Gallyas, pp. 2228-2230 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.01976.x.
| S-EPMC3448890 | biostudies-literature
Project description:Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rβ- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear β-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on β-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.
| S-EPMC8881622 | biostudies-literature
Project description:Brain pericytes not only maintain the anatomical, biochemical and immune blood-brain barrier, but display features of mesenchymal stem cells (MSCs) in vitro. MSCs have pro-regenerative properties attributed to their secretome. However, whether also brain pericytes possess such pro-regenerative capacities is largely unknown. Here we characterize the secretome and microvesicle (MV) release of human brain pericytes mediated by platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor beta (PDGFRβ) signalling. Upon PDGF-BB, pericytes release not only a plethora of growth factors and a panel of cytokines, but also MVs containing BDNF, FGFb, βNGF, VEGF and PLGF, a response that is specific for PDGFRβ signalling and activation of the ERK 1/2 pathway. In contrast, lipopolysaccharide (LPS), an activator of the innate immune system, stimulates the secretion of much higher amounts of mainly inflammatory cytokines and activates the NFκB pathway. Pericytes change their morphology and undergo opposite changes in surface marker expression, respectively. Our findings provide evidence that the secretome of human brain pericytes varies greatly depending on the exogenous stimulus. The differential secretory functions of pericytes may play an important role in either regulating neuroinflammation or contributing to neurorestoration and identify a possible new target cell for neuroregeneration.
| S-EPMC5757443 | biostudies-literature
Project description:Recombinant platelet-derived growth factor (PDGF)-BB was expressed and secreted from yeast in order to study the structure-function relationships of this mitogen. A simple purification scheme has been developed which yields greater than 95% pure PDGF-BB. Analysis of this recombinant PDGF-BB shows partial proteolysis after arginine-32. Substitution of this arginine residue, or arginine-28 [a potential KEX2 (lysine-arginine endopeptidase) cleavage site], prevents or reduces cleavage of PDGF-BB respectively. These mutations result in a 5-fold increase in expression levels of PDGF-BB, and the resulting mutant proteins show higher activity in a number of biological assays than the cleaved wildtype PDGF-BB. These data are in accord with previous work by Giese, LaRochelle, May-Siroff, Robbins & Aaronson [(1990) Mol. Cell Biol. 10, 5496-5501] suggesting that the region isoleucine-25-phenylalanine-37 is involved in PDGF-receptor binding.
| S-EPMC1130640 | biostudies-other
Project description:We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic ?-catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BB--and serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway.
| S-EPMC6295663 | biostudies-literature
Project description:BackgroundThis study aimed to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection compared with hyaluronic acid (HA) injection for patients undergoing knee osteoarthritis.MethodsWe systematically searched electronic databases including PubMed, Embase, Web of Science, and the Cochrane Library on January 23, 2020 to identify relevant studies issued in English languages. The outcomes evaluating the efficacy of knee osteoarthritis (KOA) treatment were Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (WOMAC pain, function, stiffness, and total scores) at 1, 3, 6, and 12 months; International Knee Documentation Committee (IKDC) scores, Lequesne Index score, Visual Analog Scale (VAS) scores, EQ-VAS scores, and KOOS scores. The pooled data were analyzed by Stata 12.0.ResultsA total of 20 RCTs were enrolled in the present meta-analysis. The pooled results demonstrated that platelet-rich plasma (PRP) injection reduced pain more effectively than hyaluronic acid (HA) injection at 6-month and 12-month follow-up evaluated by WOMAC pain scores and VAS scores. EQ-VAS in the patients treated with PRP injection was lower than that in patients with HA injection at 12 months. Moreover, the patients with PRP injection had a better function recovery than those with HA injection at 1-month, 3-month, 6-month, and 12-month follow-up, as evaluated by WOMAC function scores. WOMAC total scores showed significant difference at 6-month and 12-month follow-up. The IKDC scores indicated PRP injection was significantly more effective than HA injection at 3 months and 6 months. However, the Lequesne Index scores, KOOS scores, and adverse events did not show any significant difference between groups.ConclusionIntra-articular PRP injection appeared to be more efficacious than HA injection for the treatment of KOA in terms of short-term functional recovery. Moreover, PRP injection was superior to HA injection in terms of long-term pain relief and function improvement. In addition, PRP injection did not increase the risk of adverse events compared to HA injection.
| S-EPMC7488405 | biostudies-literature