Transforming Growth Factor-β Gene Family Members and Bone*

Centrella, Michael; Horowitz, Mark C.; Wozney, John M.; McCarthy, Thomas L.

doi:10.1210/edrv-15-1-27

Cited by 221 publications

(234 citation statements)

References 87 publications

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“…The Tgf-␤s are a superfamily of growth factors that comprises over two dozen related polypeptides, including the Bmps (Centrella et al, 1994;Massague et al, 1994;Cohen, 2000c). The Tgf-␤s play an essential role in many biological processes, including collagen synthesis, bone regeneration, suture patency, and eventual suture fusion (Centrella et al, 1994;Massague et al, 1994;Opperman et al, 1997Opperman et al, , 1999Opperman et al, , 2000Opperman et al, , 2002aRoth et al, 1997a,b;Cohen, 2000c;Opperman and Ogle, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The Tgf-␤s play an essential role in many biological processes, including collagen synthesis, bone regeneration, suture patency, and eventual suture fusion (Centrella et al, 1994;Massague et al, 1994;Opperman et al, 1997Opperman et al, , 1999Opperman et al, , 2000Opperman et al, , 2002aRoth et al, 1997a,b;Cohen, 2000c;Opperman and Ogle, 2002). The manipulation of these growth factors may also have clinical applications in the treatment of craniosynostosis (Roth et al, 1997b;Opperman et al, 1999Opperman et al, , 2000Opperman et al, , 2002bChong et al, 2001Chong et al, , 2002Mooney et al, 2002a;Opperman and Ogle, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…A myriad of genetic and epigenetic etiologies that produce craniosynostosis have been identified (Cohen, 1989(Cohen, , 2000aJabs, 2002), and this rabbit strain only models a small percentage of craniosynostotic cases (Mooney et al, 1994a(Mooney et al, , 1996a(Mooney et al, , 2002Cohen, 2000b). However, the highly conserved Tgf-␤3 signaling pathway for suture maintenance is probably active in the majority of these etiologies (Centrella et al, 1994;Massague et al, 1994;Cohen, 2000c;Opperman and Ogle, 2002), and can be manipulated. Variations in neurocapsular growth patterns and timing have also been observed in rabbits and humans.…”

Section: Discussionmentioning

confidence: 99%

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Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

et al. 2003

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Craniosynostosis results in cranial deformities and increased intracranial pressure, which pose extensive and recurrent surgical management problems. Developmental studies in rodents have shown that low levels of transforming growth factor-␤3 (Tgf-␤3) are associated with normal fusion of the interfrontal (IF) suture, and that Tgf-␤3 prevents IF suture fusion in a dose-dependent fashion. The present study was designed to test the hypothesis that Tgf-␤3 can also prevent or "rescue" fusing sutures in a rabbit model with familial craniosynostosis. One hundred coronal sutures from 50 rabbits with delayed-onset, coronal suture synostosis were examined in the present study. The rabbits were divided into five groups of 10 rabbits each: 1) sham controls, 2) bovine serum albumin (BSA, 500 ng) low-dose protein controls, 3) low-dose Tgf-␤3 (500 ng), 4) high-dose BSA (1,000 ng) controls, and 5) high-dose Tgf-␤3 (1,000 ng). At 10 days of age, radiopaque amalgam markers were implanted in all of the rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, the BSA or Tgf-␤3 was combined with a slow-absorbing collagen vehicle and injected subperiosteally above the coronal suture. Radiographic results revealed that high-dose Tgf-␤3 rabbits had significantly greater (P Ͻ 0.05) coronal suture marker separation than the other groups. Histomorphometric analysis revealed that high-dose Tgf-␤3 rabbits also had patent coronal sutures and significantly (P Ͻ 0.01) greater sutural widths and areas than the other groups. The results suggest that there is a dose-dependent effect of TGF-␤3 on suture morphology and area in these rabbits, and that the manipulation of such growth factors may have clinical applications in the treatment of craniosynostosis. Anat Rec Part A 274A: 962-971, 2003.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

et al. 2003

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“…Transforming growth factor-␤ (TGF-␤) 1 is stored in bone matrix as a latent form (4), is thought to be released and activated during osteoclastic bone resorption (5), and to play an important role in the regulation of bone metabolism (6). TGF-␤ is one of the most potent stimulators of the production of type I collagen in various types of cells (7,8), and the most pronounced effect of TGF-␤ in bone is the stimulation of matrix protein synthesis including type I collagen, proteoglycans, and fibronectin (9,10).…”

mentioning

confidence: 99%

Differentiation and Cell Surface Expression of Transforming Growth Factor-β Receptors Are Regulated by Interaction with Matrix Collagen in Murine Osteoblastic Cells

Takeuchi

Nakayama

Matsumoto

1996

Journal of Biological Chemistry

194

142

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Although transforming growth factor (TGF)-␤ enhances bone formation, it inhibits the differentiation of osteoblasts. To clarify the regulatory mechanism of osteoblastic differentiation and TGF-␤ actions, the relationship among differentiation, TGF-␤ actions, and matrix protein synthesis was examined using murine osteoblast-like MC3T3-E1 cells. Alkaline phosphatase (ALP) activity continued to increase during long-term cultures, and the increase was closely associated with a reduction in cell surface TGF-␤ receptors competent to bind TGF-␤. Both the stimulation of proteoglycan synthesis and the inhibition of ALP activity by TGF-␤ were also suppressed. Collagen synthesis inhibitors and an anti-␣2␤1 integrin blocking antibody blocked the changes in ALP activity and TGF-␤ receptors, and a DGEA peptide that interferes binding of collagen to ␣2␤1 integrin also blocked the increase in ALP activity. Furthermore, when MC3T3-E1 cells were cultured on extracellular matrix layers obtained from these cells, all the differentiation-associated changes could be observed without collagen production, and the extracellular matrix-induced differentiation was also blocked by an anti-␣2␤1 integrin antibody. These results demonstrate that the interaction of cell surface ␣2␤1 integrin with matrix collagen synthesized by osteoblasts themselves is involved in the osteoblastic differentiation and the reduction in cell surface receptors and actions of TGF-␤. It is suggested that matrix collagen synthesized under the stimulation by TGF-␤ plays an important role in the regulation of osteoblastic differentiation and TGF-␤ actions by differentiation-associated down-regulation of TGF-␤ receptors.Cells of osteoblast lineage exert various functions to maintain bone formation. After bone resorption, osteoblast precursors migrate and proliferate at the site of bone formation. They, then, synthesize type I collagen and other matrix proteins. Onto the newly formed unmineralized matrices, hydroxyapatite crystals are accumulated, and mineralization of bone is completed (1). In order to form lamellar bones that maintain structural integrity and physical strength, it appears to be of critical importance for osteoblastic cells to maintain sequentially ordered development of these multiple functions.Using cultured osteoblastic cells obtained from bone or of clonal origin, it has become clear that these cells express various functional properties in a differentiation-dependent manner from the early proliferation phase, via the matrix formation phase with active matrix protein synthesis, to the mineralization phase (1-3). Various hormones and cytokines are shown to affect the differentiation process and functional properties of these cells. However, the mechanism that controls the differentiation of osteoblastic cells is as yet unclear.Transforming growth factor-␤ (TGF-␤) 1 is stored in bone matrix as a latent form (4), is thought to be released and activated during osteoclastic bone resorption (5), and to play an important role in the regulation of bone meta...

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“…Since osteoblasts produce and bind TGF-ß and IL-6 (20,21), both are likely to participate in the autocrine/paracrine control of bone remodeling. TGF-ß stimulates several extracellular matrix proteins, such as fibronectin, type I collagen, and osteopontin, which are required for normal bone mineralization.…”

Section: Discussionmentioning

confidence: 99%

Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

Duarte

Carvalho

Cruz

et al. 2002

Braz J Med Biol Res

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Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin1a (IL-1a), IL-6, IL-11, tumor necrosis factor-a (TNF-a) and transforming growth factor-ß (TGF-ß) using an undecalcified plastic embedding method. Intense staining for IL-1a, IL-6, TNF-a and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

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Transforming Growth Factor-β Gene Family Members and Bone*

Cited by 221 publications

References 87 publications

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

Differentiation and Cell Surface Expression of Transforming Growth Factor-β Receptors Are Regulated by Interaction with Matrix Collagen in Murine Osteoblastic Cells

Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

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