Osteoclast differentiation in osteoporosis

An inhibitor of osteoclast differentiation and/or function is expected to be useful for treatment of bone lytic diseases such as osteoporosis, rheumatoid arthritis, and tumor metastasis into bone. Paenol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38, and NF-kB pathway (Tsai et al., 2008). Symbioimine (Fig. 32.2A) from the symbiotic marine dinoflagellate Symbiodinium sp. exhibits inhibitory effect on osteoclast differentiation (Kita et al., 2004).

Biselyngbyaside (Fig. 32.2B) has been isolated from marine cyanobac-terium Lyngbya sp. and subjected to osteoclast differentiation study. Bise-lyngbyaside inhibited RANKL-induced osteoclastogenesis in mouse monocytic RAW264 cells and primary bone marrow-derived macrophages at a low concentration (Yonezawa et al., 2011). Effects of Spirulina algae on bone metabolism in ovariectomized estrogen-deficient rats and hindlimb-unloaded mice have also been examined (Ishimi et al., 2006).

The BMD of the whole femur and tibia of ovariectomized rats in any of the Spirulina-treated groups was not significantly different from that of the ovariectomized group, although BMD of the distal femur and proximal tibia was significantly lower in the Spirulina-treated groups than in the ovariectomized group after a 6-week experimental period (Ishimi et al., 2006).

Raw264 Osteoclast

FIGURE 32.2 (A) Symbioimine, (B) biselyngbyaside, (C) ikarisoside A, (D) bolinaquinone, and (E) fucoxanthin.

FIGURE 32.2 (A) Symbioimine, (B) biselyngbyaside, (C) ikarisoside A, (D) bolinaquinone, and (E) fucoxanthin.

Inhibition of osteoclastogenic differentiation by ikarisoside A (Fig. 32.2C) in RAW 264.7 cells via JNK and NF-kB signaling pathways have been recently reported (Choi et al., 2010). Lucas et al. (2003) studied the modulatory effect of bolinaquinone (Fig. 32.2D), a marine sesquiter-penoid, on acute and chronic inflammatory processes. Fucoxanthin (Fig. 32.2E) that induces apoptosis also induced osteoclast differentiation in a study conducted by Das et al. (2010).

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