Role of carotenoid β-cryptoxanthin in bone homeostasis

Abstract

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Aging induces bone loss due to decreased osteoblastic bone formation and increased osteoclastic bone resorption. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Nutritional factors may play a role in the prevention of bone loss with aging. Among various carotenoids (carotene and xanthophylls including beta (β)-cryptoxanthin, lutein, lycopene, β-carotene, astaxanthin, and rutin), β-cryptoxanthin, which is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), has been found to have a stimulatory effect on bone calcification in vitro. β-cryptoxanthin has stimulatory effects on osteoblastic bone formation and inhibitory effects on osteoclastic bone resorption in vitro, thereby increasing bone mass. β-cryptoxanthin has an effect on the gene expression of various proteins that are related osteoblastic bone formation and osteoclastic bone resororption in vitro. The intake of β-cryptoxanthin may have a preventive effect on bone loss in animal models for osteoporosis and in healthy human or postmenopausal women. Epidemiological studies suggest a potential role of β-cryptoxanthin as a sustainable nutritional approach to improving bone health of human subjects. β-Cryptoxanthin may be an osteogenic factor in preventing osteoporosis in human subjects.

Figure 1

The cellular and molecular mechanism by which β-cryptoxanthin (BCX) stimulates bone formation and mineralization in osteoblastic cells. BCX may bind to orphan receptors in the nucleus of osteoblastic cells, and it stimulates gene expression of bone formation-related proteins. BCX also stimulates nuclear transcriptional activity mediated through activation of protein kinase C (PKC) or mitogen-activated protein kinase (MAPK) in osteoblastic cells.

Figure 2

The molecular mechanism by which β-cryptoxanthin (BCX) has suppressive effects on mature osteoclasts. BCX inhibits osteoclast formation from mononuclear osteoclasts which are mediated through RANKL and RANK signaling in bone marrow culture systems. BCX stimulates apoptotic cell death by stimulating the gene expression of caspase-3, an apoptosis-inducing enzyme, and suppression of gene expression of Bcl-2, a rescue protein of apoptosis. In addition, BCX suppresses the gene expression of TRACP and cathepsin K, which are bone resorption-related enzymes, and their enzyme activities in mature osteoclasts.