Transdifferentiation of chondrocytes into neuron‐like cells induced by neuronal lineage specifying growth factors

Greene, Carol Ann; Green, Colin; Sherwin, Trevor

doi:10.1002/cbin.10358

Cited by 7 publications

(7 citation statements)

References 22 publications

(29 reference statements)

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“… 15 In a reversal of roles, rat chondrocytes have been shown, when stimulated by neurogenic growth factors (FGF-2, Neurobasal-A, EGF, and IGF-1), to transdifferentiate into stellate neuronal cells with ablation of COL2 expression and expression of neuron-specific proteins such as NF-200, MAP-2, and β-III tubulin. 16 Another case of osteogenic transdifferentiation involves the dedifferentiation of myoblasts via BMP-2 induction of SMAD1, which is mediated by osteoactivin. Osteoactivin, in turn, downregulates myogenic markers and upregulates osteogenic markers, such as RUNX2 and ALP.…”

Section: Introductionmentioning

confidence: 99%

The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification

2018

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There is a worldwide epidemic of skeletal diseases causing not only a public health issue but also accounting for a sizable portion of healthcare expenditures. The vertebrate skeleton is known to be formed by mesenchymal cells condensing into tissue elements (patterning phase) followed by their differentiation into cartilage (chondrocytes) or bone (osteoblasts) cells within the condensations. During the growth and remodeling phase, bone is formed directly via intramembranous ossification or through a cartilage to bone conversion via endochondral ossification routes. The canonical pathway of the endochondral bone formation process involves apoptosis of hypertrophic chondrocytes followed by vascular invasion that brings in osteoclast precursors to remove cartilage and osteoblast precursors to form bone. However, there is now an emerging role for chondrocyte-to-osteoblast transdifferentiation in the endochondral ossification process. Although the concept of “transdifferentiation” per se is not recent, new data using a variety of techniques to follow the fate of chondrocytes in different bones during embryonic and post-natal growth as well as during fracture repair in adults have identified three different models for chondrocyte-to-osteoblast transdifferentiation (direct transdifferentiation, dedifferentiation to redifferentiation, and chondrocyte to osteogenic precursor). This review focuses on the emerging models of chondrocyte-to-osteoblast transdifferentiation and their implications for the treatment of skeletal diseases as well as the possible signaling pathways that contribute to chondrocyte-to-osteoblast transdifferentiation processes.

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Section: Introductionmentioning

confidence: 99%

The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification

2018

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“…Growth factors are critical in regulating transdifferentiation in conjunction with the extracellular matrix which plays a role in stabilising differentiated tissues . For example, chondrocytes cultured in a chondrocyte culture medium maintain their morphology and ability to express collagen type II . In contrast, chondrocytes cultured in a neurogenic differentiation medium acquired dendritic morphology and lost their ability to express collagen type II .…”

Section: Transdifferentiationmentioning

confidence: 99%

“…For example, chondrocytes cultured in a chondrocyte culture medium maintain their morphology and ability to express collagen type II . In contrast, chondrocytes cultured in a neurogenic differentiation medium acquired dendritic morphology and lost their ability to express collagen type II . These cells instead started expressing filament and microtubule proteins that were specific to neuronal cells .…”

Section: Transdifferentiationmentioning

confidence: 99%

“…In contrast, chondrocytes cultured in a neurogenic differentiation medium acquired dendritic morphology and lost their ability to express collagen type II . These cells instead started expressing filament and microtubule proteins that were specific to neuronal cells . Another example of growth factors on transdifferentiation can be observed with the effect of TGF‐β on mouse mammary epithelial cells in vitro .…”

Section: Transdifferentiationmentioning

confidence: 99%

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Transdifferentiation of myoblasts into osteoblasts – possible use for bone therapy

Lin

Carnagarin

Dharmarajan

et al. 2017

Journal of Pharmacy and Pharmacology

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Objectives Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful. Key findings The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation. Summary This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours.

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“…Although the isolated cells from OA cartilage had a chondrocyte phenotype, however, this phenotype was unstable in long term in vitro cultures, leading to a fibroblastic phenotype (92). These transformed cells have a dendritic morphology and altered cell metabolism (93). Instead of type II collagen, these transformed cells produce high levels of type I collagen and may have a different response from chondrocytes to the stimuli in our experiments.…”

Section: Chondrocyte Isolation and Purity Determinationmentioning

confidence: 76%

Role of chondrocyte antigen presentation in osteoarthritis

Sengprasert¹

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Osteoarthritis (OA) is an inflammatory disorder characterized by degeneration of joint components, especially the cartilage. Chondrocytes are found in articular cartilage and play a role in cartilage production and degradation. Several studies found that chondrocytes not only control the cartilage metabolism, but also play a role in immune responses. However, the role of chondrocytes in the pathogenesis of OA is still unclear. In this study, we investigated the responses of OA chondrocytes after stimulating with IFN-γ and proteoglycan aggrecan and also determined antigen presentation function of chondrocytes to present proteoglycan aggrecan peptide to T cells. We found that OA chondrocyte upregulate MHC class I and II on their cell surface after IFN-γ stimulation. Proteoglycan aggrecan peptides, especially P16-31 and P263-280, can stimulate chondrocyte to express CD80 and 86, and secrete high levels of IL-6, IL-8 and TNFα. Moreover, chondrocytes were able to present the P263-280 and P16-31 peptides to autologous T cells isolated from infrapatellar fat pads and stimulated T cell proliferation. These results indicate proteoglycan aggrecan peptides in the presence of IFN-γ induces antigen presentation function of chondrocytes. The knowledge from this study might be used as a foundation for further therapeutic development.

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Transdifferentiation of chondrocytes into neuron‐like cells induced by neuronal lineage specifying growth factors

Cited by 7 publications

References 22 publications

The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification

The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification

Transdifferentiation of myoblasts into osteoblasts – possible use for bone therapy

Role of chondrocyte antigen presentation in osteoarthritis

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