The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells

Üstünel, İ̇smail; Ozenci, A. Merter; Sahin, Zeliha; Ozbey, Ozlem; Acar, Nuray; Tanrıöver, Gamze; Çelik-Özenci, Çiler; Demir, Ramazan

doi:10.1016/j.acthis.2007.12.005

Cited by 52 publications

(46 citation statements)

References 24 publications

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“…1(a) shows that passage 0 (P0) E-MSCs expressed Notch-1 at a high rate. This marker was associated with a progenitor state in articular cartilage cell population (Hiraoka et al, 2006;Ustunel et al, 2008), and also with the ability of the Notch-1 positive cells to form colonies (Dowthwaite et al, 2004). Sca-1 and CD73, which are also expressed in bone marrow and adipose-derived MSCs (Gawronska-Kozak et al, 2007), were shown to be expressed in our E-MSCs population.…”

Section: Chondrogenic Differentiationmentioning

confidence: 68%

Influence of culture parameters on ear mesenchymal stem cells expanded on microcarriers

Sart

Schneider

Agathos

2010

Journal of Biotechnology

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Section: Chondrogenic Differentiationmentioning

confidence: 68%

Influence of culture parameters on ear mesenchymal stem cells expanded on microcarriers

Sart

Schneider

Agathos

2010

Journal of Biotechnology

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“…Several studies have suggested that the superficial zone of articular cartilage contains progenitors of articular chondrocytes. [31][32][33] Our data show that whereas transient Wnt/␤-catenin signaling increases cellularity in articular cartilage, conditional ␤-catenin ablation decreases it. In a previous study, we observed a similar loss of superficial cells after ␤-catenin loss at embryonic stages.…”

Section: Articular Cartilage Changesmentioning

confidence: 80%

Transient Activation of Wnt/β-Catenin Signaling Induces Abnormal Growth Plate Closure and Articular Cartilage Thickening in Postnatal Mice

Yuasa

Kondo

Yasuhara

et al. 2009

The American Journal of Pathology

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Wnt/␤-catenin signaling is required for skeletal development and organization and for function of the growth plate and articular cartilage. To further clarify these roles and their possible pathophysiological importance, we created a new transgenic mouse model in which Wnt/␤-catenin signaling can be activated in cartilage for specific periods of time. These transgenic mice expressed a constitutive active form of ␤-catenin fused to a modified estrogen receptor ligand-binding domain under the control of cartilage-specific collagen 11␣2 promoter/enhancer. Transient Wnt/␤-catenin signaling activation in young adult mice by tamoxifen injections induced growth retardation and severe deformities in knee joints. Tibial and femoral growth plates displayed an excessive number of apoptotic cells and eventually underwent abnormal regression. Articular cartilage exhibited an initial acute loss of proteoglycan matrix that was followed by increases in thickness, cell density, and cell proliferation. In reciprocal studies, we found that conditional ablation of ␤-catenin in postnatal mice using a Col2-CreER strategy led to hypocellularity in articular cartilage, growth plate disorganization, and a severe reduction in bone volume. Together, these data provide evidence that Wnt/␤-catenin signaling has important and distinct roles in growth plate and articular cartilage and that postnatal dysregulation of this signaling pathway causes diverse structural and functional changes in the two cartilaginous structures. (Am J

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“…Interestingly, the expression of NOTCH signaling molecules is significantly up-regulated in OA cartilage (25–27, 46), indicating a role for NOTCH in OA on-set and progression. We demonstrated here that sustained NOTCH activation in postnatal joint cartilages leads to an early and progressive OA-like pathology, including joint cartilage degradation, fibrosis, and synovial expansion, which is likely due to the dramatic up-regulation of cartilage degradation enzymes and pro-inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

A dual role for NOTCH signaling in joint cartilage maintenance and osteoarthritis

et al. 2015

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Loss of NOTCH signaling in postnatal murine joints results in osteoarthritis (OA), indicating a requirement for NOTCH during joint cartilage maintenance. Unexpectedly, NOTCH components are significantly up-regulated in human and murine post-traumatic OA, suggesting either a reparative or pathological role for NOTCH activation in OA. Here we investigated the potential dual role for NOTCH in joint maintenance and OA by generating two mouse models overexpressing the NOTCH1 intracellular domain within postnatal joint cartilage; one with sustained NOTCH activation that likely resembles pathological NOTCH signaling and one with transient NOTCH activation that more closely reflects physiological NOTCH signaling. Sustained NOTCH signaling in joint cartilage leads to an early and progressive OA pathology, while on the contrary, transient NOTCH activation enhances cartilage matrix synthesis and promotes joint maintenance under normal physiological conditions. Using RNA-seq, immunohistochemical, and biochemical approaches we identified several novel targets potentially responsible for NOTCH-mediated cartilage degradation, fibrosis, and OA progression, including components of the IL6/STAT3 and ERK/p38 MAPK pathways; factors that may also contribute to post-traumatic OA development. Collectively, these data demonstrate a dual role for the NOTCH pathway in joint cartilage and identify important downstream NOTCH effectors as potential targets for disease modifying osteoarthritis drugs (DMOADs).

show abstract

The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells

Cited by 52 publications

References 24 publications

Influence of culture parameters on ear mesenchymal stem cells expanded on microcarriers

Influence of culture parameters on ear mesenchymal stem cells expanded on microcarriers

Transient Activation of Wnt/β-Catenin Signaling Induces Abnormal Growth Plate Closure and Articular Cartilage Thickening in Postnatal Mice

A dual role for NOTCH signaling in joint cartilage maintenance and osteoarthritis

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