Fibroblast growth factor 2 and transforming growth factor β1 induce precocious maturation of articular cartilage

Khan, Ilyas; Evans, Samuel Lewin; Young, Robert D.; Blain, Emma Jane; Quantock, Andrew J.; Avery, Nicholas C.; Archer, Charles W.

doi:10.1002/art.30543

Cited by 31 publications

(32 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many efforts have been made to study the molecular signals involved in FGF-2 induced proliferation of chondrocytes [43][44][45], with the hope of preventing the formation of fibrous cartilage tissue caused by FGF-2 treatment [ 46,47]. Our data uncover a positive role of FGF-1 in proliferation of hPCs, at least in co-culture with MSCs.…”

Section: Discussionmentioning

confidence: 65%

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

Leijten

Blitterswijk

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

Previously, we showed that mesenchymal stromal cells (MSCs) in co-culture with primary chondrocytes secrete soluble factors that increase chondrocyte proliferation. The objective of this study is to identify these factors. Human primary chondrocytes (hPCs) isolated from late-stage osteoarthritis patients were co-cultured with human bone marrow-derived MSCs (hMSCs) in pellets. Genome-wide mRNA expression analysis and quantitative polymerase chain reactions (qPCR) were used to identify soluble factors that were specifically induced in co-cultures. Immunofluorescent staining combined with cell tracking and enzyme-linked immunosorbent assay (ELISA) were performed to validate up-regulation at the protein level and to identify the cellular origin of the increased proteins. Chemical blockers and neutralizing antibodies were used to elucidate the role of the identified candidate genes in co-cultures. A number of candidate factors were differentially regulated in co-cultures at the mRNA level. Of these, fibroblast growth factor-1 (FGF-1) mRNA and protein expression were markedly increased in co-cultures predominantly due to up-regulated expression in MSCs. Blocking of FGF signaling in co-culture pellets by specific FGF receptor inhibitors or FGF-1 neutralizing antibodies completely blocked hPCs proliferation. We demonstrate that MSCs increase FGF-1 secretion on co-culture with hPCs, which, in turn, is responsible for increased hPCs proliferation in pellet co-cultures. C artilage repair is among the key targets of regenerative medicine. Several stem cell-based therapies have been proposed to treat cartilage defects, rheumatic arthritis, osteoarthiris (OA), and other joint diseases. These therapeutic strategies include implantation or injection of mesenchymal stromal cells (MSCs) in the diseased joint or bone marrow stimulation techniques such as micro fracture. These procedures rely on cellular interactions between MSCs and native cells in the joint [1][2][3][4]. Recent studies showed that intra-articularly injected MSCs can reduce incidence and severity of arthritis in animal model by inducing immune tolerance [5]. Further investigations showed that MSCs are capable of inducing hyporesponsiveness of T-lymphocytes and of expressing antiinflammatory mediators in macrophages [6,7]. Besides immuno-suppressive effects, intra-articularly injected MSCs were also reported to inhibit thickening of the synovium and to protect against cartilage destruction in a mouse OA model [8]. However, with the cellular interactions between MSCs and native chondrocytes receiving less attention [9], the molecular mechanism of interactions between MSCs and native chondrocytes is poorly understood [10]. In order to maximize the benefits of stem cell therapy, these cellular interactions need to be clarified.Previous reports showed that cartilage matrix formation was increased in co-cultures of human primary chondrocytes (hPCs) with MSCs compared with monocultures [11,12]. Further investigations revealed that the inductive effects of MSCs on cartila...

show abstract

Section: Discussionmentioning

confidence: 65%

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

Leijten

Blitterswijk

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…*P < 0.05, n 04 stiff tissue is formed, which has an even distribution of PGs (Miyazaki et al 2010). A recent investigation has also shown that the combined presence of FGF-2 and TGF-β 1 accelerates maturation-type changes in tissue stiffness, collagen fibril architecture, and cross-linking, and even more importantly, the zonal fine structure is obtained only in the presence of growth factors (Khan et al 2011). Growth factors also cause a 52% reduction in the height of the explants (Khan et al 2011).…”

Section: Discussionmentioning

confidence: 90%

Five percent oxygen tension is not beneficial for neocartilage formation in scaffold-free cell cultures

Lindeberg

Ylärinne

et al. 2012

Cell Tissue Res

View full text Add to dashboard Cite

We have investigated whether 5% oxygen tension (O(2)) is beneficial for neocartilage formation when chondrocytes are cultured in transwell-COL inserts. Six million bovine primary chondrocytes were cultured in an insert with DMEM supplemented with 10% fetal bovine serum and antibiotics, with or without glucosamine sulphate (GS) in a 5% or 20% O(2) environment for 2, 4, or 6 weeks. The samples were collected for the histological staining of proteoglycans (PGs) and type II collagen, quantitative reverse transcription with the polymerase chain reaction (RT-PCR) analyses of the mRNA expression of aggrecan and procollagen α(1)(II), procollagen α(2)(I) and hyaluronan synthase 2, quantitation of PGs, and agarose gel electrophoresis. Neocartilage produced at 20% O(2) appeared larger than that at 5% O(2). Histological staining showed that more PGs and type II collagen and better native cartilage structure were produced at 20% than at 5% O(2). The thickness of neocartilage increased during the culture period. Quantitative RT-PCR showed that the procollagen α(1)(II) mRNA expression level was significantly higher at 20% than at 5% O(2). However, no significant difference in gene expression and PG content was found between control and GS-treated cultures at either 20% or 5% O(2). Thus, in contrast to monolayer cultures, engineered cartilage from scaffold-free cultured chondrocytes at 20% O(2) produced better extracellular matrix (ECM) than that at 5% O(2). PGs were mainly large. Exogenous GS was not beneficial for the ECM in scaffold-free chondrocyte cultures.

show abstract

“…It has been recently shown that molecular signalling alone can induce and enhance AC maturation in vitro. A combination of growth factors (FGF-2 and TGFβ1) induce collagen remodelling and significantly enhance (229 % increase) mechanical stiffness and change in the microanatomic structure of cartilage explants from immature calves in vitro without any loading of the construct (Khan et al, 2011). Enhanced crosslinking of the collagen fibrils is also observed.…”

Section: Wwwecmjournalorg C Cluzel Et Al Articular Cartilage Develmentioning

confidence: 97%

Foetal and postnatal equine articular cartilage development: magnetic resonance imaging and polarised light microscopy

Cluzel

Blond²,

Fontaine³

et al. 2013

eCM

View full text Add to dashboard Cite

Adult articular cartilage (AC) has a well described multizonal collagen structure. Knowledge of foetal AC organisation and development may provide a prototype for cartilage repair strategies, and improve understanding of structural changes in developmental diseases such as osteochondrosis (OC). The objective of this study was to describe normal development of the spatial architecture of the collagen network of equine AC using 1.5 T magnetic resonance imaging (MRI) and polarised light microscopy (PLM), at sites employed for cartilage repair studies or susceptible to OC. T2-weighted fast-spin echo (FSE) sequences and PLM assessment were performed on distal femoral epiphyses of equine foetuses, foals and adults. Both MRI and PLM revealed an early progressive collagen network zonal organisation of the femoral epiphyses, beginning at 4 months of gestation. PLM revealed that the collagen network of equine foetal AC prior to birth was already organised into an evident anisotropic layered structure that included the appearance of a dense tangential zone in the superficial AC in the youngest specimens, with the progressive development of an underlying transitional zone. A third, increasingly birefringent, radial layer developed in the AC from 6 months of gestation. Four laminae were observed on the MR images in the last third of gestation. These included not only the AC but also the superficial growth plate of the epiphysis. These findings provide novel data on normal equine foetal cartilage collagen development, and may serve as a template for cartilage repair studies in this species or a model for developmental studies of OC.

show abstract

Fibroblast growth factor 2 and transforming growth factor β1 induce precocious maturation of articular cartilage

Cited by 31 publications

References 48 publications

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

Fibroblast Growth Factor-1 Is a Mesenchymal Stromal Cell-Secreted Factor Stimulating Proliferation of Osteoarthritic Chondrocytes in Co-Culture

Five percent oxygen tension is not beneficial for neocartilage formation in scaffold-free cell cultures

Foetal and postnatal equine articular cartilage development: magnetic resonance imaging and polarised light microscopy

Contact Info

Product

Resources

About