β-Catenin Signaling Pathway Is Crucial for Bone Morphogenetic Protein 2 to Induce New Bone Formation

Abstract Background Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. However, the administration of bovine proteins to humans is associated with the risk of zoonotic complications. We therefore examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model. Methods A 2-mm critical-sized bone defect was created in the femur of 9-week-old male C57/BL6J mice. Mice were randomly allocated into one of four treatment groups (n = 6 each): control (no treatment), poly(POG)n only, 0.2 μg, or 2.0 μg BMP-2 with poly(POG)n. New bone formation was monitored using soft X-ray radiographs, and bone formation at the bone defect site was examined using micro-computed tomography and histological examination at 4 weeks after surgery. Results Administration of 2.0 μg of BMP-2 with poly(POG)n promoted new bone formation and resulted in greater bone volume and bone mineral content than that observed in the control group and successfully achieved consolidation. In contrast, bone formation in all other groups was scarce. Conclusions Our findings suggest the potential of BMP-2 with poly(POG)n as a material, free from animal-derived collagen, for the treatment of large bone defects.

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Overexpression of bone morphogenetic protein 2 through aberrant canonical Wnt/β-catenin signaling pathway plays an important role in heterotopic ossification of adrenal myelolipoma

Canadian Urological Association Journal ◽

10.5489/cuaj.1610 ◽

2014 ◽

Vol 8 (1-2) ◽

pp. 104 ◽

Cited By ~ 7

Author(s):

Yozo Mitsui ◽

Hiroaki Yasumoto ◽

Miho Hiraki ◽

Naoko Arichi ◽

Noriyoshi Ishikawa ◽

...

Keyword(s):

Bone Formation ◽

Heterotopic Ossification ◽

Bone Morphogenetic Protein ◽

Signaling Pathway ◽

Bone Morphogenetic Protein 2 ◽

Heterotopic Bone ◽

Heterotopic Bone Formation ◽

Adrenal Myelolipoma ◽

Morphogenetic Protein ◽

Canonical Wnt

The precise mechanism of heterotopic ossification caused by several types of tumours is largely unknown. However, recent studies have indicated that bone morphogenetic protein 2 (BMP2) is closely linked to the Wnt/β-catenin signaling pathway in this rare phenomenon of bone formation. We report a rare case of adrenal myelolipoma (ML) in a 27-year-old woman with heterotopic bone formation. Immunohistochemical findings showed BMP2 expression in the cytoplasm of tumour cells, as well as the matrix adjacent to newly developed bone tissue. In addition, β-catenin was prominent in the cytoplasm and nuclei of BMP2-positive tumour cells. To the best of our knowledge, this is the first report of adrenal ML showing heterotopic ossification with accelerated expression of both BMP2 and β-catenin. Our case findings indicate that BMP2 overexpression via aberrant canonical Wnt/β-catenin signaling may contribute to heterotopic bone formation occurring in adrenal ML.

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