Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity

Abstract

Beta-cryptoxanthin (β-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that β-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E2 production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of β-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by β-cry. In osteoblasts, β-cry inhibited PGE2 production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, β-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) β, and adding ATP canceled this IKKβ inhibition. Molecular docking simulation further suggested that β-cry binds to the ATP-binding pocket of IKKβ. In Raw264.7 cells, β-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of β-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

Effects of paprika carotenoid supplementation on bone turnover in postmenopausal women: a randomized, double-blind, placebo-controlled, parallel-group comparison study

“…Capsanthin, β-carotene, β-cryptoxanthin, and zeaxanthin are major carotenoids present in the PCE used in this study. In agreement with our findings, several studies have reported that these carotenoids inhibit osteoclastogenesis (19)(20)(21). Therefore, PCE may suppress bone resorption by decreasing the number of osteoclasts.…”

“…These epidemiological data suggest that adequate intake of carotenoids might be useful to maintain bone health. In addition, several in vitro and in vivo studies have shown that some carotenoids suppress bone resorption (19)(20)(21)(22). However, few clinical studies have focused on the role of carotenoid supplementation in bone turnover.…”

Comparing the Levels of Gingival Crevicular Fluid Prostaglandin E2 in Generalized Chronic Periodontitis Between Healthy and Type 2 Diabetes Patients: A Case-Control Study

“…Recently, some studies showed the effect of several drugs (such as melatonin, cyclic NSAID) in reduction of PGE 2 for the treatment of periodontitis in healthy and diabetic patients [26][27][28][29][30].…”

Carotenoids and Periodontal Infection

“…Ebersole et al, have reported that lower β-cryptoxanthin levels in blood were found in moderate/severe periodontitis patients [40]. Interestingly, Hirata et al, reported that β-cryptoxanthin suppressed LPS-induced osteoclasts differentiation via PGE 2 inhibition in HGFs and restored the alveolar bone loss in an experimental in vivo periodontitis models [47]. In addition, Matsumoto et al, reported that β-cryptoxanthin suppressed the osteoclast formation mediated by LPS in co-cultures of osteoblasts and bone marrow cells [34].…”

“…β-Cryptoxanthin, one of the main carotenoids, is found abundantly in fruit and vegetables such as papaya, paprika, and carrot [47]. β-Cryptoxanthin also exerts various biological activities such as antioxidant functions.…”