Hepatocyte growth factor (HGF) adsorption kinetics and enhancement of osteoblast differentiation on hydroxyapatite surfaces

Hossain, Md. Delowar; Irwin, Regina; Baumann, Melissa J.; McCabe, Laura R.

doi:10.1016/j.biomaterials.2004.07.051

Cited by 49 publications

(28 citation statements)

References 43 publications

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“…The enhanced osteogenesis could be due to an increased self-renewal of mesenchymal stem cells that leads to an increase in the number of cells that can become fully mature osteoblasts when osteogenic stimuli are present. HGF has been shown by others to stimulate the expression of early osteoblast markers (ALP activity) in preosteoblasts, 67 and has also been reported to stimulate 1,25-dihydroxyvitamin D 3 -induced osteoblast differentiation by increased proliferation of osteoblast precursors. 68 In line with the latter study, we observed a proliferative effect of HGF on hMSCs.…”

Section: Discussionmentioning

confidence: 95%

HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma

Standal

Abildgaard

Fagerli

et al. 2006

Blood

150

123

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The bone disease in multiple myeloma is caused by an uncoupling of bone formation from bone resorption. A key difference between patients with and patients without osteolytic lesion is that the latter have fewer and less active osteoblasts. Hepatocyte growth factor (HGF) is often produced by myeloma cells and is found at high concentrations in the bone marrow of patients with multiple myeloma. IntroductionAlmost all patients with multiple myeloma develop osteolytic lesions and/or diffuse osteopenia. The presence of myeloma cells in the bone marrow leads to both increased number and activity of osteoclasts as well as reduced number and dysfunction of osteoblasts. 1,2 During the early stages of the disease, enhanced osteoclast activation is at least partly compensated by an increase in bone formation. As the disease progresses, the osteoblasts are fewer and less active, so that bone resorption is uncoupled from bone formation. 3 Recently, several factors have been proposed to be involved in the dysregulation of osteoblastogenesis in multiple myeloma. [4][5][6][7] However, the mechanisms for reduced bone formation in patients with myeloma are still not completely understood.We have shown that myeloma cells produce hepatocyte growth factor (HGF). 8 Others have shown that HGF is among the most upregulated genes in myeloma cells as compared with normal plasma cells. 9 High serum concentration of HGF is associated with poor prognosis in patients with myeloma, 10 and HGF has been shown to play several roles in disease progression. [11][12][13][14][15][16] Furthermore, we have shown that HGF is found at high concentrations in bone marrow plasma from patients with myeloma. 17 In a mouse model of multiple myeloma developed in our laboratory, a prominent feature was the complete lack of osteoblasts. 18 In this model, JJN3 cells, which produce high levels of HGF, were injected into severe combined immunodeficient (SCID) mice. The concentration of HGF in the bone marrow plasma of the mice was high; in some mice the concentration exceeded 5 g/mL. 18 We therefore hypothesized that HGF can interfere with osteoblastogenesis, and thereby be a factor responsible for the reduced number and reduced activity of osteoblasts in patients with multiple myeloma. Materials and methods Cells and cell culture conditionsC2C12 cells (ATTC, Rockville, MD) were routinely maintained in Dulbecco modified Eagle medium (DMEM; Gibco, Carlsbad, CA) with 15% heat inactivated fetal calf serum (FCS; EuroClone, Pero, Italy) in a humidified atmosphere containing 5% CO 2 at 37°C. Cells were not allowed to reach confluence, and were used before they completed 8 passages. Human mesenchymal stem cells (hMSCs) were purchased from Cambrex Bio Science and routinely maintained in human mesenchymal stem cells growth media (MSCGM; Cambrex Bio Science, East Rutherford, NJ) according to the manufacturer's instructions. hMSCs were used before they completed 8 passages. Osteoblast differentiationhMSCs were seeded at 4000 cells/cm 2 and cultured until they reached 70% co...

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Section: Discussionmentioning

confidence: 95%

HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma

Standal

Abildgaard

Fagerli

et al. 2006

Blood

150

123

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“…At the fracture site, HGF induces the up-regulation of BMP receptors in mesenchymal cells during the early phase of fracture repair 17) . Furthermore, HGF was reported to stimulate osteoblast differentiation based on angiogenic properties in combination with hydroxyapatite 58,59) . Since endothelial cells can produce BMP-2 60) and osteoblasts secreted HGF 61) during bone repair, in our experimental model, endothelial cells activated by exogenous HGF may produce BMP-2 that can act on osteoblasts as an osteogenic signal, and in turn, the activated osteoblasts may secrete HGF to further promote angiogenesis.…”

Section: The Effect Of Hgf On Angiogenesis During Bone Regeneration Imentioning

confidence: 99%

Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms

Masuda

Otsu

Kumakami-Sakano

et al. 2015

J. Hard Tissue Biology.

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Promotion of bone repair contributes to the shortening of the treatment period and improvement of the therapeutic effect in large bone defects. The purpose of the present study was to determine the optimal condition for the administration of growth factors to facilitate bone repair and explore the significance of angiogenesis in bone regeneration in vivo. Critical-size calvarial defects were created in the parietal bones of adult ddY mice, and the defects were treated with gelatin sponges impregnated with growth factors BMP-2, FGF-2, and HGF, alone or in combination. The bone regeneration at 1, 2, 3, and 4 weeks was evaluated using micro-computed tomography and histological observation. Critical-size calvarial defects were also created in Flk1-GFP mice to analyze angiogenesis in the early phase of bone repair. The proliferation of Flk1-GFP positive endothelial cells during bone repair was quantitatively evaluated using immunohistochemistry for Ki67. Treatment with a combination of BMP-2 and HGF (BMP-2+HGF) significantly induced more new bone formation within the bone defects compared with the other groups. Compared with BMP-2 alone, bone regeneration was rapidly increased by BMP-2+HGF from 3 weeks of the beginning of the treatment. The number of FLK1-GFP and Ki67 double positive cells in the defect areas of mice administered BMP-2+HGF at 1 week was larger than that in those administered BMP-2 alone. These results indicate that the combination of BMP-2 and HGF was markedly efficient in bone regeneration due to the promotion of angiogenesis in the early phase of bone repair.

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“…HGF, in combination with vitamin D3, promotes growth and differentiation of human mesenchymal cells into osteogenic cells [20]. HGF enhances differentiation of osteoblasts [21] and induces the expression of BMP receptors during the early phase of fracture repair [13].…”

Section: Discussionmentioning

confidence: 99%

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

Goshima

Nakase

et al. 2012

Journal of Orthopaedic Science

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Background Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of b-tricalcium phosphate (b-TCP) and collagen in repairing segmental bone defects. Methods Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of b-TCP granules and collagen, with or without 100 lg recombinant human HGF. Biweekly, bone regeneration and b-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests. Results Compared with the bone tissue treated with b-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of b-TCP were promoted 4 weeks postoperatively by treatment with HGF in the b-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the b-TCP granules were completed in a shorter period by combining HGF with b-TCP and collagen, compared with tissues without HGF. Conclusions The combined application of HGF in a b-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and b-TCP for treatment of bone defects made a substantial difference.

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Hepatocyte growth factor (HGF) adsorption kinetics and enhancement of osteoblast differentiation on hydroxyapatite surfaces

Cited by 49 publications

References 43 publications

HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma

HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma

Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

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