Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells.

Yeh, Lee Chuan C; Adamo, Martin L.; Kitten, Allison M.; Olson, Merle S.; Lee, John C.

doi:10.1210/endo.137.5.8612532

Cited by 38 publications

(35 citation statements)

References 15 publications

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“…Compared with the control group without growth factor, addition of OP-1 stimulated an additional 10% increase in bone formation, which agrees with our previous experiment, in which OP-1 was pipetted at 330 ng/ml daily (data not shown), and studies from other laboratories demonstrating OP-1 stimulates the differentiation of osteoprogenitor cells [2,28,29,[31][32][33]. Differentiation of the osteoprogenitor cells without addition of growth factors was synchronous with an increase of OC between Days 15 and 20 followed by a slower increase later on (slope of 0.44) (Fig.…”

Section: Discussionsupporting

confidence: 91%

Controlled Release of Growth Factors on Allograft Bone in vitro

Huang

Ryu

Ren

et al. 2008

Clin Orthop Relat Res

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Allografts are important alternatives to autografts for treating defects after major bone loss. Bone growth factors have both local autocrine and paracrine effects and regulate the growth, proliferation, and differentiation of osteoprogenitor cells. To study the effects of prolonged, continuous, local delivery of growth factors on bone growth, we developed a new microelectromechanical system (MEMS) drug delivery device. Bone marrow cells from mice were seeded on mouse allograft discs and cultured in osteogenic media with osteogenic protein 1 (OP-1) and/or basic fibroblast growth factor (FGF-2) delivered from MEMS devices for 6 weeks. We monitored bone formation by changes of bone volume using micro-CT scanning and release of osteocalcin using ELISA. The data suggest the MEMS devices delivered constant concentrations of OP-1 and FGF-2 to the media. Bone marrow cells grew on the allografts and increased bone volume. Addition of OP-1 increased bone formation whereas FGF-2 decreased bone formation. Local delivery of growth factors over a prolonged period modulated the differentiation of osteoprogenitor cells on allograft bone.

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Section: Discussionsupporting

confidence: 91%

Controlled Release of Growth Factors on Allograft Bone in vitro

Huang

Ryu

Ren

et al. 2008

Clin Orthop Relat Res

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“…Further analysis is needed to determine the mechanisms by which BMP-7 and Dex regulate IGFBP-5 and FHL-2 in bone. In contrast to our observed increase in IGFBP-5 expression in human osteosarcoma cells following BMP-7 treatment, previous data have been reported that IGFBP-5 mRNA expression decreased in primary rat calvaria cells following BMP-7 treatment [38][39][40]. These data suggest that IGFBP-5 response to BMP-7 treatment may be species and/or celltype specific.…”

Section: Coordinated Expression Of Igfbp-5 Fhl-2 and Adam-9 In Respcontrasting

confidence: 99%

Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts

Govoni

Amaar

Kramer

et al. 2006

Growth Hormone & IGF Research

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The roles of insulin-like growth factors (IGFs) in regulating growth and their modulation by six IGF binding proteins (IGFBP) are well established. IGFBP-5, the most abundant IGFBP stored in bone, is an important regulator of bone formation via IGF-dependent and -independent mechanisms. Two new proteins, four and a half lim (FHL)-2, a transcription modulator that interacts with IGFBP-5, and a disintegrin and metalloprotease (ADAM)-9, an IGFBP-5 protease, have been identified as potential regulators of IGFBP-5 action in bone. We tested the hypothesis that agents which modulate bone formation by regulating IGFBP-5 expression would also regulate FHL-2 and ADAM-9 expression in a coordinated manner. We evaluated the expression of IGFBP-5, FHL-2, and ADAM-9 by real-time reverse transcriptase (RT)-PCR during differentiation of mouse bone marrow stromal cells into osteoblasts and in response to treatment with bone formation modulators in the LSaOS human osteosarcoma cell line. IGFBP-5 and FHL-2 increased 4.3-and 3.0-fold (P ≤ 0.01), respectively, during osteoblast differentiation. Dexamethasone (Dex), an inhibitor of bone formation, decreased IGFBP-5 and FHL-2 and increased ADAM-9 in LSaOS cells (P ≤ 0.05). Bone morphogenic protein (BMP)-7, a stimulator of bone formation, increased IGFBP-5 and decreased ADAM-9 (P < 0.01). To determine if BMP-7 would eliminate Dex inhibition of IGFBP-5, cells were treated with Dex + BMP-7. The BMP-7-induced increase in IGFBP-5 was reduced, but not eliminated, in the presence of Dex (P ≤ 0.01), indicating that BMP-7 and Dex may regulate IGFBP-5 via different mechanisms. Transforming growth factor (TGF)-β, a stimulator of bone formation, increased IGFBP-5 and FHL-2 expression (P ≤ 0.01). IGF-I and TNF-α decreased expression of ADAM-9 (P < 0.05). In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone.

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“…Smads up-or down-regulate the transcription of a subset of target genes that includes Runx2 (12). BMP-7, also known as the osteogenic protein-1 (OP-1), has been found to induce new cartilage and bone formation in vitro and in vivo (13-15) and regulate cell proliferation and differentiation (16,17). OP-1 blocks cartilage damage caused by Fn-f and may promote repair by enhancing proteoglycan and collagen synthesis (18).…”

mentioning

confidence: 99%

“…2 Yeh and colleagues (17,23) have presented data indicating that IGF-1 gene expression may be up-regulated by OP-1 at both transcriptional and post-transcriptional level in osteoblastic cells. IGF-1 is a polypeptide that exerts anabolic/anticatabolic effects on cartilage.…”

mentioning

confidence: 99%

Inhibitory Effects of Insulin-like Growth Factor-1 and Osteogenic Protein-1 on Fibronectin Fragment- and Interleukin-1β-stimulated Matrix Metalloproteinase-13 Expression in Human Chondrocytes

Pacione

Chubinskaya

et al. 2003

Journal of Biological Chemistry

133

170

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Matrix metalloproteinase-13 (collagenase-3), a member of the family of matrix metalloproteinases (MMPs), plays a major pathological role in the cartilage destruction of arthritis. A dramatic up-regulation of MMP-13 by inflammatory cytokines such as interleukin (IL)-1␤ or by fibronectin fragments has been observed in chondrocytes. In this study, we investigated the inhibitory effects of insulin-like growth factor-1 (IGF-1) and osteogenic protein-1 (OP-1) on the expression of MMP-13, which was induced by fibronectin fragment or IL-1␤ in human immortalized or human primary chondrocytes. IGF-1 and OP-1 each significantly reduced the basal level as well as fibronectin fragment-or IL-1␤-stimulated transcription of the MMP-13 gene in a dosedependent fashion with the corresponding decreases in the protein level of MMP-13. The most prominent suppressive effect was observed by the combination of IGF-1 and OP-1, which decreased the basal promoter activity by 60% and almost completely abrogated the fibronectin fragmentstimulated MMP-13 promoter activity. OP-1 was found to enhance mRNA levels of IGF-1 and the IGF-1 receptor, the latter of which appeared to be responsible for the combined effect of IGF-1 and OP-1. The suppressive effect of IGF-1 and OP-1 on MMP-13 expression was due in part to downregulation of the expression of pro-inflammatory cytokines and the activity of their intermediate molecules, including NF-B and AP-1 factors. We propose that IGF-1 and OP-1 could be key physiological regulators of MMP-13 gene expression and that the combination of IGF-1 and OP-1 may be useful in controlling the excess catabolic activity in arthritis.Cartilage homeostasis is a well synchronized balance between anabolic and catabolic processes. During the development of osteoarthritis, this balance is disrupted resulting in progressive degradation of the articular cartilage (1). Studies have demonstrated that members of the matrix metalloproteinase (MMP) 1 family are the major pathophysiological mediators of the cartilage destruction process in osteoarthritis (2). Recently, in vitro, clinical, and transgenic studies have provided evidence that chondrocyte MMP-13 (collagenase-3) is a leading candidate enzyme mediating the degradation of type II collagen in osteoarthritis (2-4). A dramatic up-regulation of MMP-13 gene expression in response to inflammatory cytokines, such as interleukin-1␤ (IL-1␤) (5), or by fibronectin fragment (Fn-f) (6) has been observed in chondrocytes. However, there is limited knowledge of the cellular mechanisms that regulate MMP-13 gene expression in chondrocytes. Accumulating evidence demonstrates that the bone morphogenetic proteins (BMPs), a subfamily of the transforming growth factor-␤ superfamily, are inhibitors of MMP-13 expression in human fetal chondrocytes (7) or rat osteoblast-enriched cells (8, 9). Upon ligand binding, the specific serine/threonine kinase activity of BMP receptors (type I or II) transduce signals (10) by allowing the association of Smad1 and Smad4 in the cytoplasm followed by the tran...

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Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells.

Cited by 38 publications

References 15 publications

Controlled Release of Growth Factors on Allograft Bone in vitro

Controlled Release of Growth Factors on Allograft Bone in vitro

Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts

Inhibitory Effects of Insulin-like Growth Factor-1 and Osteogenic Protein-1 on Fibronectin Fragment- and Interleukin-1β-stimulated Matrix Metalloproteinase-13 Expression in Human Chondrocytes

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