Osteoblast differentiation

Marine collagen peptides (MCP) derived from Chum Salmon (Oncor-hynchus keta) skin were investigated for the development of femurs in growing rats of both sexes (Xu et al., 2010).

The modification of chromatin structure thereby regulating gene transcription through histone deacetylases (HDACs) plays important roles in osteogenesis and is considered to be a promising potential therapeutic target for bone diseases. Largazole (Fig. 32.1A) exhibited in vitro and in vivo osteogenic activity by HDAC inhibition and significantly induced the expression of alkaline phosphatases, osteopontin expression, and increased expression of Runx2 and BMPs. Largazole showed in vivo bone-forming efficacy in the mouse calvarial bone formation assay and the rabbit calvarial bone fracture healing model (Lee et al., 2011).

Norzoanthamine (Fig. 32.1B) is a nontoxic marine alkaloid and its collagen protective activity indicates that it provides significant therapeutic benefits. Norzoanthamine accelerates the formation of a collagen-hydroxyapatite composite and enhances collagen release from an immobilized matrix vesicle model. Norzoanthamine recognizes a pep-tide chain nonspecifically and stabilizes its secondary structure, and collagen has polyvalent binding sites for norzoanthamine. Collagen-nor-zoanthamine supramolecular association is considered to be one of the most significant modes of action for enhancement of bone formation. Norzoanthamine suppressed the proteolysis not only of collagen but also of elastin and bovine serum albumin, so it apparently has a universal

FIGURE 32.1 (A) Largazole, (B) norzoanthamine, (C) dieckol, and (D) 1-(3',5'-dihydroxyphenoxy)-7-(2",4",6"-trihydroxyphenoxy) 2,4,9-trihydroxydibenzo-1,4,-dioxin.

FIGURE 32.1 (A) Largazole, (B) norzoanthamine, (C) dieckol, and (D) 1-(3',5'-dihydroxyphenoxy)-7-(2",4",6"-trihydroxyphenoxy) 2,4,9-trihydroxydibenzo-1,4,-dioxin.

protective effect of guarding extracellular matrix (ECM) proteins from degradation (Hikage et al., 1998; Kinugawa et al., 2009).

Norzoanthamine has also been isolated from zoanthid Zoanthus sp. which suppresses the decrease in bone weight and strength in ovariecto-mized mice, indicating that it could be a good candidate as an osteoporotic drug (Kuramoto et al., 1998).

Arthritis is one of the most prevalent chronic inflammatory diseases, and it is characterized by structural and biochemical changes in major tissues of the joint, including degradation of the cartilage matrix, insufficient synthesis of ECM. Ecklonia cava (EC) is a member of the family of Laminariaceae, which is an edible marine brown alga with various bioac-tivities. The methanol extracts of brown alga EC, the dieckol (Fig. 32.1C) and 1-(3',5'-dihydroxyphenoxy)-7-(2",4",6"-trihydroxyphenoxy) 2,4,9-tri-hydroxydibenzo-1,4,-dioxin (Fig. 32.1D) have been used for arthritis treatment at in vitro level (Ryu et al., 2009a).

The effect of the fractionated extracts obtained from S. horneri on bone calcium content and osteoclast-like cell formation in vitro has also been investigated. The effects of S. horneri on bone components in the femoral diaphyseal and metaphyseal tissues of young and aged rats were studied. The oral intake of the water-solubilized S. horneri extract significantly altered the bone components of young rats in vivo (Uchiyama and Yamaguchi, 2002; Uchiyama et al., 2004).

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