Anti-Osteoporotic Effects of Kukoamine B Isolated from Lycii Radicis Cortex Extract on Osteoblast and Osteoclast Cells and Ovariectomized Osteoporosis Model Mice.

Eunkuk Park,Chun Whan Choi,Ji-Won Lee,Jin-Hyok Park,Miran Jo,Jieun Kim,Wan Yi Li,Seulbi Park,Dam Huh,Hyun-Seok Jin,Jeonghyun Kim,Subin Yeo,Seon-Yong Jeong,Sang Woo Lee,Mun-Chang Kim

doi:10.3390/ijms20112784

Abstract

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

Highlights

Bone is a living organ constantly remodeled and maintained by a balance between bone formation and resorption [1,2]
Fractionation and isolation of the bioactive component from Lycii Radicis Cortex (LRC) ethanol was performed (Figure S1). 30% of the ethanol LRC extract was fractionated, and each fraction was investigated for a bone formation-enhancing effect using an alkaline phosphatase (ALP) activity assay in preosteoblast MC3T3-E1 cells for identifying the bioactive fraction (Figure S2)
ALP is a homodimeric protein enzyme located in the cell membranes of osteoblasts, and is a reliable bmoanrekemr eotaf bboolnisemmdeutraibnogliosmsteodbulraisntgdoiffseteroenbltaiasttiodnif[f2er5e].ntTiahteiorenfo[r2e5,]a. nTAheLrPefoasresa, yanwaAsLcPonadssuacytedwatos sccornedenucttheedbtiooascctirveeenfrathcteiobnisoaocntibvoenefrfaocrtimonatsioonn

Summary

Introduction

Bone is a living organ constantly remodeled and maintained by a balance between bone formation and resorption [1,2]. Bone remodeling is a physiological condition regulated by osteoblasts replacing new bone formations and osteoclasts removing old or damaged bone [1]. Osteoclasts are differentiated from mononuclear cells of the monocyte/macrophage lineage, and they break down bone tissue essential for osteoblast new bone formation. Bone formation includes the proliferation and differentiation of osteoblasts via the activation of alkaline phosphatase (ALP), collagen synthesis, and the mineralization of bone [3]. Bone resorption involves the differentiation of osteoclasts via the activation of tartrate-resistant acid phosphatase (TRAP) [4,5]. The balanced relationship between bone formation and bone resorption is critical for maintaining bone strength and preventing bone loss [6]. An imbalanced regulation of these bone-remodeling processes leads to serious bone loss via osteoporosis, a metabolic bone disease [1]

Objectives

Methods

Results

Conclusion