Injectable growth/differentiation factor‐5–recombinant human collagen composite induces endochondral ossification via Sry‐related HMG box 9 (Sox9)expression and angiogenesis in murine calvariae

Kadomatsu, Hideshi; Matsuyama, Takashi; Yoshimoto, Takehiko; Negishi, Yoichi; Sekiya, Hiroo; Yamamoto, Masahide; Izumi, Yuichi

doi:10.1111/j.1600-0765.2007.01023.x

Cited by 20 publications

(15 citation statements)

References 33 publications

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“…On the other hand, these data may also imply that exogenous rhGDF-5 treatment heals defects via classical endochondral ossification, while the defects enhanced with rhBMP-2 may heal through intramembranous ossification. In fact, these observations are supported by a number of reports in the literature where it is demonstrated that bone repairs with exogenous rhGDF-5 treatment initiated endochondral ossification (Erlacher et al 1998b;Bai et al 2004;Kakudo et al 2007;Kadomatsu et al 2008). At the same time, other studies from the literature have reported that chondrogenic and osteogenic lineage pathways in response to rhGDF-5 treatment are dose and carrier dependent (Spiro et .…”

Section: Discussionsupporting

confidence: 75%

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

Wulsten

Glatt

Ellinghaus

et al. 2011

eCM

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This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP) family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF)-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue.Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

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Section: Discussionsupporting

confidence: 75%

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

Wulsten

Glatt

Ellinghaus

et al. 2011

eCM

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“…Several studies revealed that GDF-5 plays a pivotal role in a variety of musculoskeletal processes including endochondral ossification [33,34], joint formation [11,35], tendon and ligament maintenance and repair [36,37]. In addition, GDF-5 has been demonstrated to play a role in osteogenesis and ectopic bone formation [12][13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

Growth/differentiation Factor-5 Induces Osteogenic Differentiation of Human Ligamentum Flavum Cells through Activation of ERK1/2 and p38 MAPK

Zhong

Chen

Zhang

et al. 2010

Cell Physiol Biochem

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Ossification of ligamentum flavum (OLF) is a pathological ectopic ossification in the spinal ligament, leading to spinal canal stenosis, but little was known about its pathogenesis. A previous study has found growth/differentiation factor (GDF)-5 expression at ossified sites of the ligaments from OLF patients. This study aimed to investigate the osteogenic effects of GDF-5 on cultured human ligamentum flavum cells (LFCs). LFCs were isolated from human spinal ligamentum flavum, and treated with or without recombinant human (rh) GDF-5. Alkaline phosphatase (ALP) activity was measured. Expression of osteocalcin was assessed by reverse transcriptase-PCR, Western blotting and immunofluorescence. Matrix mineralization was assessed by alizarin red staining. Activation of mitogen-activated protein kinases (MAPK) ERK1/2, p38 and JNK were detected by Western blotting. We found that rhGDF-5 treatment increased ALP activity and osteocalcin expression in a time-and dosedependent manner, and induced mineralized nodule form. In addition, rhGDF-5 challenge mediated the ERK1/2 and p38 activation but not JNK. Inhibiting this activation pharmacologically, using U0126, a ERK1/ 2 inhibitor, or SB203580, a p38 inhibitor, resulted in significantly lower ALP activity and osteocalcin protein expression. The present study shows that rhGDF-5 induces osteogenic differentiation of human LFCs through activation of ERK1/2 and p38 MAPK. These findings give some new insight into the pathogenesis of OLF.

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“…In vitro and in vivo studies suggested that the administration of GDF-5 with suitable carriers induced the formation of tendon-/ligament-like and cartilage/bone-like tissues in some rodents, ruminants and primates [4][5][6]. For bone tissue engineering GDF-5 has been used in combination with scaffolds such as collagen [5,7,8] or mineralized collagen [9] which, however, do not provide any biomechanical stability. Therefore, in a weight bearing situation additional stabilization is required [10].…”

Section: Introductionmentioning

confidence: 97%

The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold

Kasten

Beyen

Bormann³

et al. 2010

Biomaterials

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Injectable growth/differentiation factor‐5–recombinant human collagen composite induces endochondral ossification via Sry‐related HMG box 9 (Sox9)expression and angiogenesis in murine calvariae

Abstract: These results suggest that rhCI seems to allow the release of rhGDF-5 and that rhGDF-5-rhCI composite induces endochondral ossification via Sox9 expression and angiogenesis in murine calvariae.

Cited by 20 publications

References 33 publications

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

Growth/differentiation Factor-5 Induces Osteogenic Differentiation of Human Ligamentum Flavum Cells through Activation of ERK1/2 and p38 MAPK

The effect of two point mutations in GDF-5 on ectopic bone formation in a β-tricalciumphosphate scaffold

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