A newly-found osteogenic enhancing molecule for bone regeneration

Bone regeneration and augmentation procedures, as necessary pre-prosthetic treatments, often require cues of osteogenesis-inducing factors for successful outcome. Previously, we found a new function of an amino-acid derivative (AAD) to recover suppressed function of osteogenic cells under a certain unfavorable condition.

Objective: This study examined the potential of AAD as an osteogenic enhancing molecule in vitro and in vivo.

Methods: Rat bone marrow-derived osteoblasts were cultured in the media with various concentrations of AAD (0ìg/ml, 400ìg/ml and 800ìg/ml) or 200ng/ml of bone morphogenic protein-2 (BMP-2). Osteoblastic phenotypes were assessed by alkaline phosphatase (ALP) activity, Von Kossa mineralizing nodule stain, and RT-PCR gene expression analysis. Osteogenic capacity of AAD was investigated using an in vivo augmentation model in the rat femur, where tissue grew into the hollow chamber titanium ring (Ö2.0mm x 1.5mm in height) beyond the cortical bone level. Collagen sponges were used as a carrier to deliver AAD into the hollow.

Results: ALP activity at day 5 and Von Kossa mineral deposition at day 14 were significantly elevated in the culture with AAD up to 6.0 times compared to that on the control culture (p<0.01). The AAD addition upregulated the expression of bone-related genes, particularly osteocalcin, at day 14 of culture up to 3.0 times. These osteoblastic functional enhancements by AAD overwhelmed those induced in the BMP-2-added culture. Micro CT morphometry revealed that bone volume in the augmentation chamber significantly increased by 100% with the AAD-containing collagen-sponge compared to that with collagen sponge alone (p<0.01). The de novo bone with the AAD addition was characterized by thicker and denser trabecular structures.

Conclusion: The amino-acid derivative enhanced the function of osteoblastic cells in vitro and osteogenic capacity in vivo. There should be an enthusiastic exploration of this molecule toward the clinical application as an osteogenic enhancer during bone regenerative therapies.