Heparin Potentiates the in Vivo Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

Zhao, Baohong; Katagiri, Takenobu; Toyoda, Hiromitsu; Takada, Takatora; Yanai, Tomoko; Fukuda, Tsuyoshi; Chung, Ung‐il; Koike, Tatsuya; Takaoka, Kunio; Kamijo, Ryutaro

doi:10.1074/jbc.m511039200

Cited by 257 publications

(252 citation statements)

References 31 publications

(54 reference statements)

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“…Heparin contained in HCF may prevent potential loss of GF bioactivity. In the presence of heparin, degradation of bone morphogenetic protein (BMP-2) is blocked, and the half-life of BMP-2 in culture media is increased 20-fold (Zhao et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

et al. 2011

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Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.

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Section: Discussionmentioning

confidence: 99%

Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

et al. 2011

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“…Heparin has been shown previously to potentiate the osteogenic effect of BMP-2. (53) Equibiaxial mechanical stretching force (10% maximum strain, 0.5-Hz frequency) was applied to the cells for 24 or 48 hours, after which the cells were collected for gene expression analysis. As shown in Fig.…”

Section: Mechanical Strain Induces Opg Expression In C2c12 Cells and mentioning

confidence: 99%

Mechanical stretching induces osteoprotegerin in differentiating C2C12 precursor cells through noncanonical Wnt Pathways

Chen

et al. 2010

Journal of Bone and Mineral Research

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Mechanical loading is known to be important for maintaining the formation and resorption rates of bone. To study the mechanisms by which mechanical loading regulates osteogenesis, we investigated the role of the Wnt pathway in C2C12 cells committed to osteogenic differentiation in response to cyclic mechanical stretching. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL to inhibit osteoclastogenesis and resorption of bone. Our results demonstrate that stretching leads to a sustained increase in OPG expression in C2C12 cells. The expression of osteogenic marker genes, such as osteocalcin and alkaline phosphatase, was transiently decreased by stretching at 24 hours and returned to control levels at 48 hours. The addition of inhibitors of the canonical Wnt/b-catenin pathways, such as the secreted FZD-related peptide sRFP2, as well as siRNA-mediated knockdown, did not inhibit the effect of stretching on OPG expression. In contrast, treatment with inhibitors of noncanonical Wnt signaling, including KN93, and siRNA for Nemo-like kinase (NLK) blocked most of the mechanical inductive effect on OPG. Furthermore, stretching-induced OPG production in the culture medium was able to inhibit the osteoclast formation of bone marrow macrophages. These results suggest that mechanical stretching may play an important role in bone remodeling through the upregulation of OPG and that the mechanical signaling leading to OPG induction involves the noncanonical Wnt pathway. ß

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“…The PCR was performed using Platinum Pfx DNA polymerase (Invitrogen) as described (28). The primer sets used were previously described (29).…”

Section: Methodsmentioning

confidence: 99%

Dual Roles of Smad Proteins in the Conversion from Myoblasts to Osteoblastic Cells by Bone Morphogenetic Proteins

Nojima

Kanomata

Takada

et al. 2010

Journal of Biological Chemistry

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Bone morphogenetic proteins (BMPs) induce ectopic bone formation in muscle tissue in vivo and convert myoblasts such that they differentiate into osteoblastic cells in vitro. We report here that constitutively active Smad1 induced osteoblastic differentiation of C2C12 myoblasts in cooperation with Smad4 or Runx2. In floxed Smad4 mice-derived cells, Smad4 ablation partially suppressed BMP-4-induced osteoblast differentiation. In contrast, the BMP-4-induced inhibition of myogenesis was lost by Smad4 ablation and restored by Smad4 overexpression. A nuclear zinc finger protein, E4F1, was identified as a possible component of the Smad4 complex that suppresses myogenic differentiation in response to BMP signaling. In the presence of Smad4, E4F1 stimulated the expression of Ids. Taken together, these findings suggest that the Smad signaling pathway may play a dual role in the BMP-induced conversion of myoblasts to osteoblastic cells.

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Heparin Potentiates the in Vivo Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

Cited by 257 publications

References 31 publications

Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

Mechanical stretching induces osteoprotegerin in differentiating C2C12 precursor cells through noncanonical Wnt Pathways

Dual Roles of Smad Proteins in the Conversion from Myoblasts to Osteoblastic Cells by Bone Morphogenetic Proteins

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