ArticleMechanisms of development
Transglutaminase 2 regulates early chondrogenesis and glycosaminoglycan synthesis.
Article in Mechanisms of development. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- TGFβ1-Induced Transglutaminase-2 Triggers Catabolic Response in Osteoarthritic Chondrocytes by Modulating MMP-13.Tissue engineering and regenerative medicine · 2021Article
- Down-Regulation of Transglutaminase 2 Stimulates Redifferentiation of Dedifferentiated Chondrocytes through Enhancing Glucose Metabolism.International journal of molecular sciences · 2017Article
- Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.Amino acids · 2017Review
- Transglutaminase 2--a novel inhibitor of adipogenesis.Cell death & disease · 2015Article
- Transglutaminase regulation of cell function.Physiological reviews · 2014Review
- Transglutaminase 2 as a novel activator of LRP6/β-catenin signaling.Cellular signalling · 2013Article
- In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.Stem cell reviews and reports · 2013Article
- Induction of chondrogenic differentiation in mesenchymal stem cells by TGF-beta cross-linked to collagen-PLLA [poly(L-lactic acid)] scaffold by transglutaminase 2.Biotechnology letters · 2013Article
- Two sides of MGP null arterial disease: chondrogenic lesions dependent on transglutaminase 2 and elastin fragmentation associated with induction of adipsin.The Journal of biological chemistry · 2013Article
- Tissue-specific responses to loss of transglutaminase 2.Amino acids · 2013Article
- Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model.PloS one · 2013Article
- A genome-wide screen indicates correlation between differentiation and expression of metabolism related genes.PloS one · 2013Article
- Tissue transglutaminase regulates chondrogenesis in mesenchymal stem cells on collagen type XI matrices.Amino acids · 2012Article
- Characterization of the transglutaminase gene family in zebrafish and in vivo analysis of transglutaminase-dependent bone mineralization.Amino acids · 2012Article
- Transglutaminase 2-mediated activation of β-catenin signaling has a critical role in warfarin-induced vascular calcification.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Cellular functions of tissue transglutaminase.International review of cell and molecular biology · 2012Review
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The expression pattern for tissue transglutaminase (TG2) suggests that it regulates cartilage formation. We analyzed the role of TG2 in early stages of chondrogenesis using differentiating high-density cultures of mesenchymal cells from chicken limb bud as a model. We demonstrate that TG2 promotes cell differentiation towards a pre-hypertrophic stage without inducing precocious hypertrophic maturation. This finding, combined with distinctive up-regulation of extracellular TG2 in the pre-hypertrophic cartilage of the growth plate, indicates that TG2 is an autocrine regulator of chondrocyte differentiation. We also show that TG2 regulates synthesis of the cartilaginous glycosaminoglycan (GAG)-rich extracellular matrix. Elevated levels of TG2 down-regulate xylosyltransferase activity which mediates the key steps in chondroitin sulfate synthesis. On the contrary, inhibition of endogenous transglutaminase activity in differentiating chondrogenic micromasses results in increased GAG deposition and enhancement of early chondrogenic markers. Regulation of GAG synthesis by TG2 appears independent of TGF-β activity, which is a downstream mediator of the TG2 functions in some biological systems. Instead, our data suggest a major role for cAMP/PKA signaling in transmitting TG2 signals in early chondrogenic differentiation. In summary, we demonstrate that matrix synthesis and early stages of chondrogenic differentiation are regulated through a novel mechanism involving TG2-dependent inhibition of PKA. These findings further advance understanding of cartilage formation and disease, and contribute to cartilage bioengineering.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.