Glycosaminoglycans promote osteogenesis from human induced pluripotent stem cells via neural crest induction

Abstract

The stepwise development of bone is rigidly controlled from mesenchymal cells through osteoblasts. Dysregulation of this process causes various bone diseases, such as osteoporosis and osteogenesis imperfecta. Recently, it has been noted that the decrease in bone density due to aging occurs not only in the axial skeleton but also in the facial bone. To address this issue, we focused on neural crest-derived osteoblasts that form craniofacial bone, and evaluated several functional ingredients that have been reported to activate osteoblast function using mineralization ability as an index. Glucosamine is a major component of glycosaminoglycans, is highly expressed in connective and cartilage tissues, and is known as a health food that improves joint function. Recent studies suggest that glucosamine promotes osteoblast activation; however, the underlying mechanism of this phenomenon remains unclear. This study is the first to elucidate the effects of glucosamine on neural crest-derived osteoblast differentiation using human induced pluripotent stem cells. We confirmed that glucosamine promotes osteogenesis of neural crest-derived mesenchymal stromal cells and osteoblasts. Furthermore, glucosamine increased the gene expression as well as the protein levels of osteopontin (OPN) and screlostin (SOST) which are involved in the following two processes: (1) conversion of mesenchymal stromal cells into osteoblasts, and (2) maturation of osteoblasts. These findings suggest that glucosamine plays a role in promoting osteogenesis and contributes to maintaining a healthy bone condition.