Abstract
The natural pure compound obtusilactone A (OA) was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP) activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.
Highlights
Cinnamomum kotoense Kanehira & Sasaki is a small evergreen tree endemic to Lanyu Island, Taiwan, is used as a dietary supplement, and its constituents exhibit various bioactivities, such as anti-proliferation and anti-tumoral activities against HeLa cells [1]
Bone marrow-derived mesenchymal stem cells (BMSCs)-based bone tissue engineering with effective osteoinductive factors are necessary for enhancing new bone formation and bone regeneration [5,6,7]
We first determined the cytotoxic effect of the pure compounds of Cinnamomum kotoense Kanehira & Sasaki via an LDH leakage test
Summary
Cinnamomum kotoense Kanehira & Sasaki is a small evergreen tree endemic to Lanyu Island, Taiwan, is used as a dietary supplement, and its constituents exhibit various bioactivities, such as anti-proliferation and anti-tumoral activities against HeLa cells [1]. The pure compounds isokotomolide A, secokotomolide A, obtusilactone A (OA) and (-)-sesamine have been extracted from C. kotoense recently. We recently reported that OA exerts effective radical scavenging activity that is comparable to vitamin C [3]. The osteoinductive effect of the pure compounds of C. kotoense, including OA, on osteogenic cells remains undefined. The differentiation of BMSCs into osteogenic/osteoprogenitor cells is a promising therapeutic method to promote new bone formation and heal fractures. The direct application of BMSCs in open surgery has been reported with encouraging results in patients with delayed bone fracture healing [5]. BMSC-based bone tissue engineering with effective osteoinductive factors are necessary for enhancing new bone formation and bone regeneration [5,6,7]
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