Abstract
Excessive bone loss occurs in inflammatory disorders such as periodontitis and osteoporosis. The underlying mechanism is related to the differentiation of macrophages into multinucleated giant osteoclasts and their bone resorptive activity. C-Phycocyanin (C-PC) is a phycobiliprotein extracted from the blue-green algae, which has been shown to have various pharmacological effects. The role of C-PC on bone metabolism needs revelation. In this study, we determined the effectiveness of C-PC as an inhibitor of osteoclast differentiation, activity, and survival in vitro. We found that C-PC strongly inhibited the differentiation of macrophages to TRAP-positive osteoclasts, distinctive osteoclast specific podosomal organization, and dentine matrix resorption without any cytotoxicity. Also, it suppressed the expression of osteoclast specific markers, such as cathepsin K and integrin β3 at mRNA and protein levels. RANKL mediated signaling utilizes reactive oxygen species (ROS) for the differentiation of osteoclasts. C-PC attenuated RANKL stimulated ROS. Mechanistic studies indicate that C-PC has the potential to reduce osteoclast formation via blocking the degradation of cytosolic IκB-α and hence, the activation of downstream markers such as c-Fos and NFATc1. However, it does not have any effect on osteoblast-mediated bone formation in vitro. Collectively, our data suggest that C-PC may be utilized as a therapeutic agent that can target bone loss mediated by excessive osteoclastic bone resorption without affecting osteoblastic activity in bone.
Highlights
Bone remodeling is a physiologically orchestrated process in which a simultaneous interplay between bone resorption and bone formation facilitates the development and maintenance of the skeletal tissues
RANKL-RANK-mediated signaling mechanisms are essential for osteoclast differentiation[10]
We evaluated the ability of C-Phycocyanin (C-PC) to inhibit osteoclast differentiation from RAW cells
Summary
Bone remodeling is a physiologically orchestrated process in which a simultaneous interplay between bone resorption and bone formation facilitates the development and maintenance of the skeletal tissues. Upon binding of RANKL to RANK, a series of downstream signaling is activated, including the activation of the NF-κB pathway This activation invokes the stimulation of c-Fos, which activates the nuclear factor of activated T cells cytoplasmic 1 (NFATc1), a master regulator of osteoclastogenesis[11,14,15]. Targeting such a signaling pathway may restrain the differentiation of osteoclasts, which could present an effective treatment strategy for osteolytic inflammatory diseases. C-PC has demonstrated anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages It interferes with the degradation of the cytosolic IκB-α after lipopolysaccharide stimulation, which suppresses the activation of the NF-κB pathway[24]. These data suggest an anti-osteoclastogenic role of C-PC that can be utilized to prevent inflammatory bone loss
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