The Response of Periodontal Ligament Cells to Fibronectin

Kapila, Yvonne L.; Lancero, Hope; Johnson, Paul W.

doi:10.1902/jop.1998.69.9.1008

Cited by 70 publications

(62 citation statements)

References 50 publications

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“…Likewise, proteolytic fragmentation of fibronectin may result from proteolysis by such MMPs as MMP1, -2, and -3, or by elastase (Wysocki and Grinnell, 1990;Grinnell and Zhu, 1994;Fukai et al, 1995). The resulting peptides regulate several cellular functions, including cell proliferation, chemotaxis (Kapila et al, 1998), migration (Schor et al, 1999), apoptosis (Kapila et al, 1999), and MMP expression in a manner that differs from that of the full-length native molecule. For example, in synovial fibroblasts, fibronectin fragments, but not intact fibronectin, can induce MMP-1 and MMP-3 expression by signaling through the oa5il1 integrin (Werb et al, 1989;Damsky et al, 1992;.…”

Section: (F) Proteolytic Degradation Of Ecm Molecules Regulates Mmp Ementioning

confidence: 99%

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Steffensen

Häkkinen

Larjava

2001

Critical Reviews in Oral Biology & Medicine

186

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During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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Section: (F) Proteolytic Degradation Of Ecm Molecules Regulates Mmp Ementioning

confidence: 99%

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Steffensen

Häkkinen

Larjava

2001

Critical Reviews in Oral Biology & Medicine

186

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“…Under these conditions, an altered matrix can result from proteolytic cleavage or alternative splicing of matrix molecules. In inflammation, proteolysis of extracellular matrix molecules leads to the formation of fragments, such as fibronectin (FN) 1 fragments, that elicit cellular responses different from those elicited by the intact molecule (1)(2)(3)(4)(5). For example, disease-associated fragments of FN trigger p53-mediated apoptosis of primary cells, but the intact molecule does not (6 -8).…”

mentioning

confidence: 99%

JNK1 and JNK2 Oppositely Regulate p53 in Signaling Linked to Apoptosis Triggered by an Altered Fibronectin Matrix

Tafolla

Wang

Wong

et al. 2005

Journal of Biological Chemistry

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The extracellular matrix regulates many cellular processes, including survival, and alterations in the matrix or in matrix survival signals can trigger apoptosis. Previously, we showed that an altered fibronectin matrix triggers apoptosis in primary cells via a novel pathway regulated by transcriptionally mediated decreases in p53 and c-Myc levels. Here we report that this apoptotic mechanism is propagated by decreased phosphorylation of focal adhesion kinase (FAK), which is linked to increased phosphorylation of c-Jun N-terminal kinase (JNK) and to decreased levels of p53. FAK is physically and spatially linked to JNK and p53, which relocalize from the nucleus to the cell membrane to mediate this interaction. Further, p53 participates in a feedback mechanism with JNK to regulate this apoptotic process and is oppositely regulated by JNK1 and JNK2.Alterations in the extracellular matrix during inflammation, development, or metastatic processes can alter the cellular biology that governs these processes. Under these conditions, an altered matrix can result from proteolytic cleavage or alternative splicing of matrix molecules. In inflammation, proteolysis of extracellular matrix molecules leads to the formation of fragments, such as fibronectin (FN) 1 fragments, that elicit cellular responses different from those elicited by the intact molecule (1-5). For example, disease-associated fragments of FN trigger p53-mediated apoptosis of primary cells, but the intact molecule does not (6 -8). Similarly, alternatively spliced variants of FN elicit different cell responses, and specific domains of FN regulate cell survival (4, 5).Previously we reported that an altered FN matrix triggers apoptosis in primary cells via a novel pathway that is regulated by transcriptionally mediated decreases in p53 and c-Myc levels in primary cells (5). To further decipher this apoptotic pathway, we explored the possible connections between integrin/FAK-mediated signals and the down-regulation of p53. We hypothesized that c-Jun N-terminal kinase (JNK) might be at the crossroads of this signaling pathway, since FAK and associated focal adhesion proteins (Rac1/Pak1/MKK4/JNK) have been linked to p53 status in the apoptosis of primary cells (9, 10). In addition, JNK can phosphorylate (11) and form a complex with p53 to stabilize it (12-16), thereby influencing its activity directly.FAK is an integrin-associated protein tyrosine kinase that is important in integrin signaling. Its activation, triggered by increased phosphorylation of Tyr 397 and other sites, has been implicated in many cellular processes, including cell survival. The N-terminal domain of FAK directs interactions with integrins and growth factor receptors. FAK also has a central catalytic domain, which contains Tyr 397 , a major autophosphorylation site and a site of interaction with the Src homology 2 domain. Its C-terminal noncatalytic domain, also known as FAK-related non-kinase (FRNK), contains sites for multiple protein-protein interactions and a focal adhesion targeting (FA...

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“…FN and COLL1 are components of the extracellular matrix (ECM) in the PDL (Lukinmaa et al 1991), and are considered markers for fibroblastic cells (Hou and Yaeger 1993). It has been reported that FN increases the proliferation rate of PDL cells (Kapila et al 1998), which led to the suggestion that FN is associated with PDL regeneration, although the functions of FN in the PDL are virtually unknown. OPN exists in many tissues, and is a component of the bone ECM.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Periodontal Ligament Cell Lines from Temperature-Sensitive Simian Virus 40 Large T-antigen Transgenic Rats

Kubota¹,

Chiba²,

Obinata³

et al. 2004

Cytotechnology

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Orthodontic tooth movement is controlled by various cell types in the periodontal ligament (PDL). Mechanical stresses, such as orthodontic force, are thought to induce differentiation of the mesenchymal cells in the PDL into osteoblasts and cementoblasts. The details of the process of differentiation, however, are not known, in part because adequate in vitro systems for their study do not yet exist. The purpose of this study was to establish and characterize immortalized PDL cell lines derived from the PDL of transgenic rats harboring the temperaturesensitive simian virus 40 T-antigen gene (TG rats). The PDL was removed from the molar roots of TG rats and incubated in tissue culture. Outgrowth cells from the PDL explant were passaged and cloned, depending on the shape of the colonies formed. The cell lines thus established were analyzed by reverse transcription-polymerase chain reaction for expression of type-I collagen, osteopontin, fibronectin, alkaline phosphatase (bone type), bone sialoprotein, the receptor activator of NF-B ligand, and osteoprotegerin. In addition, the capacity for formation of mineralized nodules was assessed by incubating cells in calcification-promoting medium at 37 C. A total of 15 stable cell lines were successfully established and characterized. These cell lines were classified into six groups based on their pattern of gene expression at 33 C. Moreover, three of these clones were capable of forming calcified nodules. In conclusion, differential gene expression was demonstrated in 15 established PDL cell lines. Some cells had the potential to differentiate into cell types found in mineralized tissues, such as osteoblasts and cementoblasts, as well as cells expressing molecules that regulate osteoclast differentiation.Abbreviations: ALP -Alkaline phosphatase; BSP -Bone sialoprotein; COLL1 -Type-I collagen; DEX -Dexamethasone; FN -Fibronectin; OPG -Osteoprotegerin; OPN -Osteopontin; PDLPeriodontal ligament; RANKL -Receptor activator of NF-B ligand; TG rats -Transgenic rats harboring the temperature-sensitive simian virus 40 T-antigen gene

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The Response of Periodontal Ligament Cells to Fibronectin

Cited by 70 publications

References 50 publications

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

JNK1 and JNK2 Oppositely Regulate p53 in Signaling Linked to Apoptosis Triggered by an Altered Fibronectin Matrix

Establishment of Periodontal Ligament Cell Lines from Temperature-Sensitive Simian Virus 40 Large T-antigen Transgenic Rats

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