Expression of fibrillins and other microfibril-associated proteins in human bone and osteoblast-like cells

Kitahama, Shinji; Gibson, Mark; Hatzinikolas, George; Hay, Shelley; Kuliwaba, J.S.; Evdokiou, Andreas; Atkins, Gerald J.; Findlay, David M.

doi:10.1016/s8756-3282(00)00292-1

Cited by 56 publications

(48 citation statements)

References 41 publications

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“…In line with previous studies (Arteaga-Solis et al, 2001;Keene et al, 1991;Kitahama et al, 2000;Quondamatteo et al, 2002;Zhang et al, 1995), we have found that fibrillin-1 and fibrillin-2 are expressed during osteoblast differentiation and secreted into the extracellular matrix. Importantly, we demonstrate that fibrillin-1 is also proteolytically processed during osteoclastic resorption, resulting in several specific degradation products, which were identified in cell culture, as well as in the extracts of human vertebral bone.…”

Section: Discussionsupporting

confidence: 93%

“…Fibrillins constitute the backbone of extracellular microfibrils, which confer structural and functional integrity to all tissues including the skeleton (Hubmacher et al, 2006;Ramirez et al, 2007). In the skeletal system, the fibrillins are expressed in long bones, ribs, vertebral bodies and cartilage (Arteaga-Solis et al, 2001;Keene et al, 1991;Kitahama et al, 2000;Quondamatteo et al, 2002;Sabatier et al, 2011;Zhang et al, 1995). Fibrillins and fibrillin-containing microfibrils regulate the bioavailability of growth factors of the TGFb superfamily including TGFb and bone morphogenetic proteins (BMPs) (Neptune et al, 2003;Nistala et al, 2010b;Sengle et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism

Tiedemann

Boraschi-Diaz

Rajakumar

et al. 2013

Journal of Cell Science

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SummaryMutations in the fibrillin-1 gene give rise to a number of heritable disorders, which are all characterized by various malformations of bone as well as manifestations in other tissues. However, the role of fibrillin-1 in the development and homeostasis of bone is not well understood. Here, we examined the role of fibrillin-1 in regulating osteoclast differentiation from primary bone-marrow-derived precursors and monocytic RAW 264.7 cells. The soluble N-terminal half of fibrillin-1 (rFBN1-N) strongly inhibited osteoclastogenesis, whereas the C-terminal half (rFBN1-C) did not. By contrast, when rFBN1-N was immobilized on calcium phosphate, it did not affect osteoclastogenesis but modulated osteoclast resorptive activity, which was evident by a larger number of smaller resorption pits. Using a panel of recombinant sub-fragments spanning rFBN1-N, we localized an osteoclast inhibitory activity to the 63 kDa subfragment rF23 comprising the N-terminal region of fibrillin-1. Osteoclastic resorption led to the generation of small fibrillin-1 fragments that were similar to those identified in human vertebral bone extracts. rF23, but not rFBN1-N, was found to inhibit the expression of cathepsin K, matrix metalloproteinase 9 and Dcstamp in differentiating osteoclasts. rFBN1-N, but not rF23, exhibited interaction with RANKL. Excess RANKL rescued the inhibition of osteoclastogenesis by rFBN1-N. By contrast, rF23 disrupted RANKL-induced Ca 2+ signaling and activation of transcription factor NFATc1. These studies highlight a direct dual inhibitory role of N-terminal fibrillin-1 fragments in osteoclastogenesis, the sequestration of RANKL and the inhibition of NFATc1 signaling, demonstrating that osteoclastic degradation of fibrillin-1 provides a potent negative feedback that limits osteoclast formation and function.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism

Tiedemann

Boraschi-Diaz

Rajakumar

et al. 2013

Journal of Cell Science

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“…The finding that MAGP-2 can interact with the fibrillins is plausible considering that the fibrillins are coexpressed with MAGP-2 in a number of tissues including lung, heart, and skeletal muscle (38), 2 osteoblasts and bone (42), and the glomerular mesangium (43). Moreover, immunoelectron microscopy studies have demonstrated colocalization of MAGP-2 and fibrillin-containing microfibrils in the bovine nuchal ligament, dermis, aortic adventitia, glomerular mesangium, and perimysium (44).…”

Section: Discussionmentioning

confidence: 91%

Microfibril-associated Glycoprotein-2 Interacts with Fibrillin-1 and Fibrillin-2 Suggesting a Role for MAGP-2 in Elastic Fiber Assembly

Penner

Rock

Kielty

et al. 2002

Journal of Biological Chemistry

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“…Cells were then treated with 5 ng/ml of TGF␤ or were left untreated. After 48 hours, supernatants, cell lysates, and extracellular matrix were prepared for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis similar to that described by Kitahama et al (25).…”

Section: Methodsmentioning

confidence: 99%

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

Kissin¹,

Lemaire²,

Korn³

et al. 2002

Arthritis & Rheumatism

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Objective. Fibrillin, an extracellular matrix protein implicated in dermal fibrosis, is increased in the reticular dermis of systemic sclerosis (SSc) skin. We undertook this study to investigate the hypothesis that transforming growth factor ␤ (TGF␤) or other cytokines regulate fibrillin matrix formation by normal and SSc fibroblasts. We further investigated the mechanism of TGF␤-induced fibrillin fibrillogenesis and its relationship to myofibroblasts.Methods. Fibrillin and fibronectin matrix deposition and ␣-smooth muscle actin expression by fibroblast cultures from normal and SSc skin treated with TGF␤ or other cytokines were analyzed by immunofluorescence. Supernatant and extracellular matrix from normal and SSc fibroblasts treated with or without TGF␤ were evaluated by Western blot and Northern blot for fibrillin protein and messenger RNA (mRNA) expression, respectively.Results. Immunofluorescence demonstrated increased fibrillin matrix formation by normal and scleroderma fibroblasts after TGF␤ treatment. Other cytokines, including tumor necrosis factor ␣, interleukin-1␤ (IL-1␤), IL-4, granulocyte-macrophage colonystimulating factor, and platelet-derived growth factor, did not affect fibrillin fibrillogenesis. Fibrillin matrix formed in proximity to myofibroblasts and independently of up-regulation of fibronectin matrix or cell number. Western blot analysis of extracellular matrix confirmed increased fibrillin after TGF␤ stimulation of normal or scleroderma fibroblasts. However, TGF␤ did not alter the expression of either soluble fibrillin protein or fibrillin mRNA.Conclusion. Our data show that TGF␤ induces fibrillin protein incorporation into the extracellular matrix without affecting fibrillin gene expression or protein synthesis, suggesting that fibrillin matrix assembly is regulated extracellularly. TGF␤ might increase fibrillin matrix by activating myofibroblasts. Such TGF␤-mediated effects could account for the increased fibrillin matrix observed in SSc skin.

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Expression of fibrillins and other microfibril-associated proteins in human bone and osteoblast-like cells

Cited by 56 publications

References 41 publications

Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism

Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism

Microfibril-associated Glycoprotein-2 Interacts with Fibrillin-1 and Fibrillin-2 Suggesting a Role for MAGP-2 in Elastic Fiber Assembly

Transforming growth factor β induces fibroblast fibrillin‐1 matrix formation

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