Icariin Has a Synergistic Effect on the Osteoinductivity of Bone Morphogenetic Protein 2 at Ectopic Sites

Abstract

Objective: Establishing biocompatible, biodegradable, osteoconductive, and osteoinductive bone materials remains a challenging subject in the research of bone healing and bone regeneration. Previously, we demonstrated the osteogenic and osteoconductive effects of biomimetic calcium phosphate (BioCaP) incorporating with Icariin and/or bone morphogenetic protein 2 (BMP-2) at orthotopic sites.

Methods: By implanting the BioCaP granules incorporated Icariin and/or BMP-2 into the dorsal subcutaneous pockets of adult male Sprague-Dawley (S-D) rats (6-7 weeks old), we investigated the osteoinductive efficacy of the samples. Micro-computed tomography(micro-CT) observations and histological slices were used to verify the osteoinduction of this system on the 2^nd and 5^th week. Statistical significances was evaluated using Turkey's post hoc test of one-way analysis of variance.

Results: The osteoinduction of the BioCaP incorporated with BMP-2 or both agents was confirmed as expected. BioCaP with Icariin alone could not generate bone formation at an ectopic sites. Nevertheless, co-administration of Icariin increased bone mineral density (BMD; p < 0.01) (628mg HA/cm³ vs 570mg HA/cm³ ) and completely changed the distribution of newly formed bone when compared with the granules with BMP-2 alone, even though there was no significant difference in the volume of newly formed bone. In contrast, the BioCaP with both agents (37.86%) had significantly fewer remaining materials than the other groups by the end of the fifth week (53.22%, 53.62% and 48.22%) (p < 0.01).

Conclusion: The co-administration of Icariin and BMP-2 increased BMD changed the distribution of newly formed bone, and reduced the amount of remaining materials. Therefore, Icariin can stimulate BMP-2 when incorporated into BioCaP granules at ectopic sites, which makes it useful for bone tissue engineering.

Keywords: Biomimetic calcium phosphate; Bone morphogenetic protein 2 (BMP-2); Ectopic sites; Icariin; Osteoinductive.