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Effect of dual treatment with SDF-1 and BMP-2 on ectopic and orthotopic bone formation.

Lee CH, Jin MU, Jung HM, Lee JT, Kwon TG - PLoS ONE (2015)

Bottom Line: The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.SDF-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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

ABSTRACT

Purposes: The 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 methods: Various 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.

Results: SDF-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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus

Histological findings of orthotopic bone formation after treatment with various concentrations of SDF-1 with/without BMP2.(A) Representative histological sections 4 weeks post-surgery (trichrome staining, ×40 in the box). (B) Bone formation ratio (%) and newly formed bone area (mm2) were analyzed histomorphometrically. Concomitant BMP-2 and SDF-1 treatment did not significantly activate orthotopic bone formation compared to independent treatment with BMP-2 or SDF-1 alone (*, p < 0.05).
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pone.0120051.g004: Histological findings of orthotopic bone formation after treatment with various concentrations of SDF-1 with/without BMP2.(A) Representative histological sections 4 weeks post-surgery (trichrome staining, ×40 in the box). (B) Bone formation ratio (%) and newly formed bone area (mm2) were analyzed histomorphometrically. Concomitant BMP-2 and SDF-1 treatment did not significantly activate orthotopic bone formation compared to independent treatment with BMP-2 or SDF-1 alone (*, p < 0.05).

Mentions: Histological analysis revealed that treatment with SDF-1 resulted in the formation of statistically insignificant amounts of new bone (0.1, 0.5, and 1μg doses resulted in 0.01 ~0.21mm2 of new bone). Consistent with the soft X-ray imaging results, BMP-2 treatment was found to induce significant amounts of new bone formation in terms of new bone area (6.6 ± 2.1mm2) and ratio (31.6 ± 4.9%) in cranial bone defects; however, this induction was not enhanced by the addition SDF-1. No statistical differences were observed in bone formation among the BMP-2-treated groups with different doses of SDF-1 (Fig. 4).


Effect of dual treatment with SDF-1 and BMP-2 on ectopic and orthotopic bone formation.

Lee CH, Jin MU, Jung HM, Lee JT, Kwon TG - PLoS ONE (2015)

Histological findings of orthotopic bone formation after treatment with various concentrations of SDF-1 with/without BMP2.(A) Representative histological sections 4 weeks post-surgery (trichrome staining, ×40 in the box). (B) Bone formation ratio (%) and newly formed bone area (mm2) were analyzed histomorphometrically. Concomitant BMP-2 and SDF-1 treatment did not significantly activate orthotopic bone formation compared to independent treatment with BMP-2 or SDF-1 alone (*, p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363323&req=5

pone.0120051.g004: Histological findings of orthotopic bone formation after treatment with various concentrations of SDF-1 with/without BMP2.(A) Representative histological sections 4 weeks post-surgery (trichrome staining, ×40 in the box). (B) Bone formation ratio (%) and newly formed bone area (mm2) were analyzed histomorphometrically. Concomitant BMP-2 and SDF-1 treatment did not significantly activate orthotopic bone formation compared to independent treatment with BMP-2 or SDF-1 alone (*, p < 0.05).
Mentions: Histological analysis revealed that treatment with SDF-1 resulted in the formation of statistically insignificant amounts of new bone (0.1, 0.5, and 1μg doses resulted in 0.01 ~0.21mm2 of new bone). Consistent with the soft X-ray imaging results, BMP-2 treatment was found to induce significant amounts of new bone formation in terms of new bone area (6.6 ± 2.1mm2) and ratio (31.6 ± 4.9%) in cranial bone defects; however, this induction was not enhanced by the addition SDF-1. No statistical differences were observed in bone formation among the BMP-2-treated groups with different doses of SDF-1 (Fig. 4).

Bottom Line: The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.SDF-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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

ABSTRACT

Purposes: The 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 methods: Various 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.

Results: SDF-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.

Conclusions: These 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.

No MeSH data available.


Related in: MedlinePlus