Enhanced Activity of Transforming Growth Factor β1 (TGF-β1) Bound to Cartilage Oligomeric Matrix Protein

Haudenschild, Dominik R.; Hong, Eunmee; Yik, Jasper H.N.; Chromy, Brett A.; Mörgelin, Matthias; Snow, Kaylene D.; Acharya, Chitrangada; Takada, Yoshikazu; Cesare, Paul E. Di

doi:10.1074/jbc.m111.234716

Cited by 68 publications

(88 citation statements)

References 44 publications

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“…51 THBS4 mediates cell-to-cell and cell-to-matrix interactions within the ECM. 52–54 COMP and LAMC3 also orchestrate TGFβ signaling, 55,56 which we show to be important for stimulation of neo-meniscus tissue.…”

Section: Discussionmentioning

confidence: 64%

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Grogan

Duffy

Pauli

et al. 2018

Journal Orthopaedic Research

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Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype. RNA was isolated from either the tissue directly or following cell isolation and 2 weeks in monolayer culture. RNA was hybridized on human genome arrays. Differentially expressed (DE) genes were identified by ranking analysis. DAVID pathway analysis was performed and visualized using STRING analysis. Quantitative PCR (qPCR) on additional donor menisci (tissues and cells) were used to validate array data. Avas cells cultured in 3D were subjected to qPCR to compare with the array-generated data. A total of 387 genes were DE based on differentiation state (>3-fold change; p < 0.01). In Avas-cultured cells, the upregulated pathways included focal adhesion, ECM-receptor interaction, regulation of actin cytoskeleton, and PDGF Signaling. In 3D-cultured Avas cells, TGFβ1 or combinations of TGFβ1 and BMP6 were most effective to promote an Avas tissue phenotype. THBS2 and THBS4 expression levels were identified as a means to denote meniscus cell phenotype status. We identified the key gene expression profiles, new markers and pathways involved in characterizing the Avas meniscus phenotype in the native state and during in vitro dedifferentiation and redifferentiation. These data served to screen 3D conditions to generate meniscus-like neotissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1947-1958, 2018.

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Section: Discussionmentioning

confidence: 64%

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Grogan

Duffy

Pauli

et al. 2018

Journal Orthopaedic Research

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“…Very recently, COMP was shown to enhance the cellular response to TGF␤ (66), which is considered a pivotal player in the pathophysiology of these disease states (67,68). Thus, COMP could be directly involved in the persistent activation of fibroblasts, leading to the excessive deposition of altered collagen fibrils.…”

Section: Discussionmentioning

confidence: 99%

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

Agarwal

Zwolanek

Keene

et al. 2012

Journal of Biological Chemistry

124

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Background:What is the biological function of COMP in skin ECM? Results: COMP binds collagens XII and XIV that associate with collagen I fibrils. All three proteins localize to anchoring plaques. Conclusion: COMP acts as an adapter in ECM of healthy skin, organizing the dermal collagen network. Significance: COMP organizes collagen I fibrils into a suprastructure that may contribute to stabilizing cohesion between the upper dermis and the basement membrane zone.

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“…COMP binds TGF-b1, BMP-2, -4, and -7 using its carboxyterminal domain. This binding enhances TGF-b1 and BMP-2 signaling in human bone mesenchymal stem cells (Haudenschild et al 2011;Ishida et al 2013), but inhibits BMP-2 signaling in vascular smooth muscle cells by preventing BMP-2 binding to its receptors (Du et al 2011). COMP thus regulates TGF-b signaling in a cell-type-specific fashion.…”

Section: Cartilage Oligomeric Matrix Protein (Comp)mentioning

confidence: 99%

Agonists and Antagonists of TGF-β Family Ligands

Chang

2016

Cold Spring Harb Perspect Biol

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The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

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Enhanced Activity of Transforming Growth Factor β1 (TGF-β1) Bound to Cartilage Oligomeric Matrix Protein

Cited by 68 publications

References 44 publications

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

Agonists and Antagonists of TGF-β Family Ligands

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