Sequential induction of marrow stromal cells by FGF2 and BMP2 improves their growth and differentiation potential in vivo

Kaewsrichan, Jasadee; Wongwitwichot, Paweena; Chandarajoti, Kasemsiri; Chua, Kien Hui; Ruszymah, B H I

doi:10.1016/j.archoralbio.2010.09.003

Cited by 19 publications

(15 citation statements)

References 34 publications

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“…Bone metabolism is essential for the development and maintenance of bone, which is mainly regulated by bone‐forming osteoblasts and bone‐resolving osteoclasts. Osteoblasts originating from mesenchymal stem cells are differentiated by various osteogenic growth factors, such as bone morphogenetic protein‐2 (BMP‐2) and fibroblast growth factor‐2 (FGF‐2) . They upregulate the expression and function of Runt‐related transcription factor 2 (Runx2), which is an essential transcription factor for osteoblast differentiation, skeletal development, and morphogenesis .…”

Section: Introductionmentioning

confidence: 99%

Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Park

Kim

Yang

et al. 2017

Journal of Bone and Mineral Research

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Peptidoglycan fragments released from gut microbiota can be delivered to the bone marrow and affect bone metabolism. We investigated the regulation of bone metabolism by muramyl dipeptide (MDP), which is a shared structural unit of peptidoglycans. Increased bone and mineral density by enhanced bone formation were observed in mice administered with MDP. Remarkably, pretreatment or posttreatment with MDP alleviated bone loss in RANKL-induced osteoporosis mouse models. MDP directly augmented osteoblast differentiation and bone-forming gene expression by Runx2 activation. Despite no direct effect, MDP indirectly attenuated osteoclast differentiation through downregulation of the RANKL/osteoprotegerin (OPG) ratio. MDP increased the expression of the MDP receptor, Nod2, and MDP-induced bone formation and osteoblast activation did not occur during Nod2 deficiency. Other Nod2 ligands also increased bone formation through the induction of Runx2, as MDP did. In conclusion, we suggest that MDP is a novel inducer of bone formation that could potentially be a new therapeutic molecule to protect against osteoporosis. © 2017 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Park

Kim

Yang

et al. 2017

Journal of Bone and Mineral Research

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“…[32] Currently, the use of rhBMP-2 has been considered as potentially beneficial in improving the surgical outcomes in ONFH treatment. [21] Thus, we investigated whether the risk of HO formation would be increased when rhBMP-2 was used in combination with the bone grafting procedure in the treatment of ONFH and whether rhBMP-2 might improve the clinical efficacy of this procedure.…”

Section: Discussionmentioning

confidence: 99%

“…[20] The complication of HO formation is associated with the physiological activity of BMPs that induces new bone formation both at ectopic and orthotopic sites. [21] Such complications are usually reported in cases with spinal fusion healing; however, little data are available from trials with respect to complications of rhBMP-2 usage in ONFH.…”

Section: Introductionmentioning

confidence: 99%

Heterotopic ossification related to the use of recombinant human BMP-2 in osteonecrosis of femoral head

et al. 2017

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Despite the wide use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in bone defect, its application in treating osteonecrosis of femoral head (ONFH) is yet to be elucidated. The heterotopic ossification (HO) after rhBMP-2 usage in some orthopedic surgeries has been reported previously; however, only a few studies describe this complication in the treatment of ONFH.The present study investigated whether the rhBMP-2 application would increase the risk of HO formation in selected ONFH patients with nonvascularized bone grafting surgery and enhance the surgical results of nonvascularized bone grafting as compared to patients who did not receive intraoperative rhBMP-2.A retrospective analysis was performed on 94 patients (141 hips) who, with Association Research Circulation Osseous (ARCO) stages IIb, IIc, and IIIa ONFH, underwent nonvascularized bone grafting surgery. The first 46 patients (66 hips) received intraoperative rhBMP-2. The postoperative radiographic results (X-ray and CT scan) and Harris hip score (HHS) were reviewed in each patient to record the incidence of HO formation and evaluate the clinical efficacy of rhBMP-2, respectively.HO formation frequently occurred in patients receiving intraoperative rhBMP-2 (8/66 hips) than those not receiving the protein (1/75 hips) (P = .02). HHS improved from preoperatively at the final follow-up (P < .01) in the BMP-positive group, with a survival rate of 83.3%. In the BMP-negative group, the HHS improved from preoperatively at the end of the follow-up (P < .01), and the survival rate was 72.0%.rhBMP-2 has osteoinductive property and might serve as an adjuvant therapy in the surgical treatment of ONFH. However, the incidence of HO formation might increase when used in high doses.

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“…Growth factors such as vascular endothelial growth factor (VEGF) [10,11] and fibroblast growth factor-2 (FGF-2) [12, 13] have been used concomitantly with BMP-2 to yield higher levels of bone regeneration compared with the use of BMP-2 alone. Recently, the role of stromal cell-derived factor-1 (SDF-1), a chemokine known to mobilize mesenchymal cells to injured tissue, in BMP-2-mediated osteoblastic differentiation was highlighted [14].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dual Treatment with SDF-1 and BMP-2 on Ectopic and Orthotopic Bone Formation

et al. 2015

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PurposesThe potent stem cell homing factor stromal cell-derived factor-1 (SDF-1) actively recruits mesenchymal stem cells from circulation and from local bone marrow. It is well established that bone morphogenetic protein-2 (BMP-2) induces ectopic and orthotopic bone formation. However, the exact synergistic effects of BMP-2 and SDF-1 in ectopic and orthotopic bone regeneration models have not been fully investigated. The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.Materials and MethodsVarious doses of SDF-1 were loaded onto collagen sponges with or without BMP-2.These sponges were implanted into subcutaneous pockets and critical-size calvarial defects in C57BL/6 mice. The specimens were harvested 4 weeks post-surgery and the degree of bone formation in specimens was evaluated by histomorphometric and radiographic density analyses. Osteogenic potential and migration capacity of mesenchymal cells and capillary tube formation of endothelial cells following dual treatment with SDF-1 and BMP-2 were evaluated with in vitro assays.ResultsSDF-1-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance BMP-2-induced ectopic and orthotopic bone regeneration. In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone.ConclusionsThese findings imply that sequence-controlled application of SDF-1 and BMP-2 must be further investigated for the enhancement of robust osteogenesis in bone defects.

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Sequential induction of marrow stromal cells by FGF2 and BMP2 improves their growth and differentiation potential in vivo

Cited by 19 publications

References 34 publications

Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Heterotopic ossification related to the use of recombinant human BMP-2 in osteonecrosis of femoral head

Effect of Dual Treatment with SDF-1 and BMP-2 on Ectopic and Orthotopic Bone Formation

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