Bone is a dynamic tissue that undergoes continual adaptation during vertebrate life to preserve skeletal size, shape, and structural integrity and to regulate mineral homeostasis. Bone mass is regulated through osteoclasts and osteoblasts. Bone mass is reduced through decreased osteoblastic bone formation and increased osteoclastic bone resorption. This decrease induces osteoporosis. Bone loss is also caused in various pathophysiologic states including inflammatory condition, obesity, diabetes, and cancer cell bone metastasis. It is affecting more than 200 million people worldwide.
This skeletal renewal is a very delicate balance between the bone resorbing osteoclasts and the bone forming osteoblasts. Osteoclasts form from precursors that circulate among the monocyte lineage and differentiate into osteoclasts under the influence of the key osteoclastogenic cytokine receptor activator of nuclear factor κ B (NF-κB) ligand (RANKL). Activation of the NF-κB signal transduction pathway by RANKL is an essential step in osteoclast differentiation and function and pharmacological antagonists of NF-κB activation repress osteoclastogenesis in vitro and bone resorption in vivo. By contrast, activation of NF-κB signaling by inflammatory cytokines such as TNFα potently inhibits osteoblast differentiation and function in vitro and in vivo. By contrast, suppression of NF-κB promotes osteoblast differentiation and mineralization in vitro and bone formation at baseline and in in vivo models of estrogen deficiency and of fracture repair.
Honokiol is a small-molecule polyphenol isolated from the genus Magnolia and has been found to have anti-angiogenic, anti-inflammatory, and anti-tumor properties in preclinical models, with low toxicity. Biochemically, honokiol has been recognized to regulate NF-κB signaling and to block TNFα-induced NF-κB activation, IκBα phosphorylation, and IκBα degradation. Consistent with this anti-NF-κB activity honokiol was found to inhibit RANKL-induced osteoclastogenesis in vitro and to inhibit the progression of collagen-induced arthritis (an animal model of the infl ammatory autoimmune disease, rheumatoid arthritis) in vivo, by down-regulating inflammatory cytokines, matrix metalloproteinases and blocking oxidative tissue damage.
Given the capacity of honokiol to antagonize NF-κB activation we examined whether honokiol could promote osteoblast differentiation and mineralization in vitro. The study data confirmed this notion and suggest that honokiol may indeed have significant potential for use as a bone anabolic agent.
You can find the study completed in 2011 here.