Phenotypic Plasticity of Human Articular Chondrocytes

Tallheden, Tommi; Dennis, James E.; Lennon, Donald P.; Sjögren‐Jansson, Eva; Caplan, Arnold I.; Lindahl, Anders

doi:10.2106/00004623-200300002-00012

Cited by 146 publications

(121 citation statements)

References 35 publications

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“…After washing with distilled H 2 O, samples were quickly dehydrated by adding 100% EtOH prior to microscopic inspection for mineralization as described earlier. 17 F. Cell viability hESCs were seeded onto a 24 well plate at a density of 10 000 cells/well. Cells were incubated in growth medium with or without the presence of metal oxides for 24 h to allow for attachment.…”

Section: E Von Kossa Stainingmentioning

confidence: 99%

Mg-corrosion, hydroxyapatite, and bone healing

et al. 2017

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The different capacities of magnesium in the metallic form (Mg-metal) and magnesium oxide (MgO) to stimulate bone healing are possible clues in the search for products that may promote bone healing. Since both Mg-metal and MgO can be assumed to release comparable amounts of Mg2+ ions during their reactions in the tissue where they have been implanted, it is of some importance to follow this process and analyze the resulting mineral formation in the tissue at the implantation site. Implants of MgO were inserted into rat tibia, and the bone healing was compared with sham-operated controls. Samples were taken after 1 week of healing and analyzed by histology, environmental scanning electron microscopy equipped with an energy dispersive x-ray spectroscopy analyzer, and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Callus bone was seen in sham-operated controls after 1 week of healing. Implantation of MgO impaired the callus bone formation by replacing bone with apparently mineralized areas, lacking osteocytes and were denoted, amorphous bodies. Elemental analysis showed increased levels of Ca (7.1%), P (3.7%), and Mg (0.2%) in the bone marrow of MgO-treated animals versus sham-operated controls Ca (2.4%), P (2.3%), and Mg (0.1%). The Ca content of the cortical bone was also significantly increased (Ca, 29% increase) in MgO-treated animals compared to sham-operated controls. The Ca content of the cortical bone of sham-operated animals was also significantly (p < 0.05) higher than the corresponding value of untreated animals, which means that the surgical trauma induces an altered composition of the bone mineral. The Ca/P ratio was 1.26–1.68, which is compatible with that of mineralized bone with different contents of organic materials. Analysis of bone sections using ToF-SIMS showed the presence of hydroxyapatite (HA) and MgCO3 in the bone marrow and in cortical bone. Analysis using x-ray photoelectron spectroscopy of Mg, MgO, and MgCO3 after incubation with cell culture medium (DMEM), in vitro, showed binding of CaPO4 at the Mg and MgO samples. The Ca/P ratio was 0.8, indicating a higher P content than that expected for HA. Exposure of human embryonic stem cells to Mg species preincubated in DMEM resulted in HA production by the cells. Thus, two sources of CaPO4 in the bone marrow of MgO-treated bone were defined, catalytic formation on Mg-species and synthesis from activated stem-cells. The presented data suggest that bone healing near Mg implants is congruent with the fracture healing of bone, boosted by high HA levels in the bone marrow. In this context, the different capacities of Mg-metal and MgO to catalyse the formation of HA can be important clues to their different bone promoting effects.

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Section: E Von Kossa Stainingmentioning

confidence: 99%

Mg-corrosion, hydroxyapatite, and bone healing

et al. 2017

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“…The identification of the ticity increased with passage and time in culture, that is to say with dedifferentiation level (3,13,39,40). Howcell types present in the fetal spinal cell population would help to answer this question.…”

Section: Adipogenic Differentiation Of Fetal Cellsmentioning

confidence: 99%

Plasticity of Fetal Cartilaginous Cells

et al. 2010

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Tissue-specific stem cells found in adult tissues can participate in the repair process following injury. However, adult tissues, such as articular cartilage and intervertebral disc, have low regeneration capacity, whereas fetal tissues, such as articular cartilage, show high regeneration ability. The presence of fetal stem cells in fetal cartilaginous tissues and their involvement in the regeneration of fetal cartilage is unknown. The aim of the study was to assess the chondrogenic differentiation and the plasticity of fetal cartilaginous cells. We compared the TGF-β3-induced chondrogenic differentiation of human fetal cells isolated from spine and cartilage tissues to that of human bone marrow stromal cells (BMSC). Stem cell surface markers and adipogenic and osteogenic plasticity of the two fetal cell types were also assessed. TGF-β3 stimulation of fetal cells cultured in high cell density led to the production of aggrecan, type I and II collagens, and variable levels of type X collagen. Although fetal cells showed the same pattern of surface stem cell markers as BMSCs, both type of fetal cells had lower adipogenic and osteogenic differentiation capacity than BMSCs. Fetal cells from femoral head showed higher adipogenic differentiation than fetal cells from spine. These results show that fetal cells are already differentiated cells and may be a good compromise between stem cells and adult tissue cells for a cell-based therapy.

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“…In culture media containing fetal bovine serum (FBS), primary keratocytes rapidly lose their characteristic phenotype, but in reduced serum supplemented with fibroblast growth factor-2 (FGF), keratocytes proliferate and maintain expression of their phenotypic markers (11). Serial passage in reduced serum-FGF medium, nevertheless, led to a slower, but inexorable, loss of the keratocyte phenotype (11).In the past decade, several studies have documented, in a variety of adult tissues, the presence of cells maintaining an ability to divide and give rise to fully differentiated daughter cell populations (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In some tissues, these cells exhibit pluripotent potential for differentiation into any of several different cell types and as such constitute true adult stem cells (23)(24)(25).…”

mentioning

confidence: 99%

PAX6 expression identifies progenitor cells for corneal keratocytes

et al. 2005

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Keratocytes of the corneal stroma produce a transparent extracellular matrix required for vision. During wound-healing and in vitro, keratocytes proliferate, becoming fibroblastic, and lose biosynthesis of unique corneal matrix components. This study sought identification of cells in the corneal stroma capable of assuming a keratocyte phenotype after extensive proliferation. About 3% of freshly isolated bovine stromal cells exhibited clonal growth. In low-mitogen media, selected clonal cultures displayed dendritic morphology and expressed high levels of keratan sulfate, aldehyde dehydrogenase 3A1, and keratocan, molecular markers of keratocyte phenotype. In protein-free media, both primary keratocytes and selected clonal cells aggregated to form attachment-independent spheroids expressing elevated levels of those marker molecules. The selected clonal cells exhibited normal karyotype and underwent replicative senescence after 65-70 population doublings; however, they continued expression of keratocyte phenotypic markers throughout their replicative life span. The progenitor cells expressed elevated mRNA for several genes characteristic of stem cells and also for genes expressed during ocular development PAX6, Six2, and Six3. PAX6 protein was detected in the cultured progenitor cells and a small number of stromal cells in intact tissue but was absent in cultured keratocytes and fibroblasts. Cytometry demonstrated PAX6 protein in 4% of freshly isolated stromal cells. These results demonstrate the presence of a previously unrecognized population of PAX6-positive cells in adult corneal stroma that maintain the potential to assume a keratocyte phenotype even after extensive replication. The presence of such progenitor cells has implications for corneal biology and for cell-based therapies targeting corneal scarring. Keywords cornea; keratan sulfate; stem cell Transparency of the cornea is conferred by the highly organized extracellular matrix of the corneal stroma. Parallel bundles of collagen fibers of highly uniform diameter are tightly packed in lamellae lying parallel to the corneal surface. A group of cornea-specific proteoglycans associate with stromal collagen effecting a supramolecular structure permitting transmission of light (1-3). Keratocytes, quiescent cells of neural crest origin, lie sandwiched between the stromal lamellae, extending dendritic processes to form an interconnected cellular network throughout the tissue (4). Keratocytes are responsible for deposition of the stromal extracellular matrix during late embryonic development, and these cells continue to maintain the integrity of the transparent matrix in the adult.In response to wounds, infections, and various chronic corneal pathologies, keratocytes become motile, mitotically active, and adopt a fibroblastic phenotype in which they secrete fibrotic Early studies of keratocytes in vitro described these cells as growing with a typical fibroblastic morphology and rapidly ceasing the secretion of keratan sulfate, a glycosaminoglycan present...

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Phenotypic Plasticity of Human Articular Chondrocytes

Cited by 146 publications

References 35 publications

Mg-corrosion, hydroxyapatite, and bone healing

Mg-corrosion, hydroxyapatite, and bone healing

Plasticity of Fetal Cartilaginous Cells

PAX6 expression identifies progenitor cells for corneal keratocytes

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