Anti-osteoporosis effect of 5-bromo-2-(4-chlorobenzoyl)-(Z)-3-(2-cyano-3-hydroxybut-2-enonyl)aminobenzo[b]furan: a novel selective estrogen receptor modulator.

The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as β-estradiol (E(2)). Here, we examined the point of action on the anti-osteoporotic effects of MU314. MU314 (10 nM) suppressed lacunae formation by osteoclastic cells and ICI-182,780, a pure E(2) antagonist, inhibited this effect.

Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity.

A reaction of 2-acetyl-3-acylaminobenzo[b]furans (9d-o) with Vilsmeier (VM) reagent afforded a mixture of (E)- and (Z)-{(E)-2-aralkenylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo-formylmethylene group on the oxazine ring. The Z-isomer was more stable than the E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two different conditions to obtain various butadiene derivatives (12) containing benzo[b]furo[3,2-d][1,3]oxazine skeleton.

A novel oxazine ring closure reaction affording (Z)-((E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)acetaldehydes and their anti-osteoclastic bone resorption activity.

A novel oxazine ring formation method was established using the reaction of 2-acetyl-(E)-3-styrylcarbonylaminobenzo[b]furans (4) with Vilsmeier-Haack-Arnold reagent to afford (E and Z)-((E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)acetaldehydes (5). (Z)-4-(8-Bromo-(E)-2-styrylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylideno)but-(E)-2-enoic acid ethyl ester (6b), derived from (Z)-5a, showed significantly potent anti-osteoclastic bone resorption activity comparable to 17beta-estradiol (E2).

Osteoporosis requires bone-specific statins.

Remedies for primary osteoporosis are increasing in brands but not always with concomitant improvements in efficacy and safety. Clinical studies suggest that nitrogen-containing bisphosphonates alone display sufficient practical effectiveness to survive as effective therapy. However, their less effectiveness in highly osteopenic patients due to their lack of genuine bone anabolic effect waits improvements.

Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.

Runx2 and phosphatidylinositol 3-kinase (PI3K)-Akt signaling play important roles in osteoblast and chondrocyte differentiation. We investigated the relationship between Runx2 and PI3K-Akt signaling. Forced expression of Runx2 enhanced osteoblastic differentiation of C3H10T1/2 and MC3T3-E1 cells and enhanced chondrogenic differentiation of ATDC5 cells, whereas these effects were blocked by treatment with IGF-I antibody or LY294002 or adenoviral introduction of dominant-negative (dn)-Akt.

Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling.

Cell migration is a key event in repair and remodeling of skeletal tissues, but the mechanism of osteoblast migration has not been resolved. Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, increase bone. However, the effect of statins on osteoblast migration remains to be clarified.

[Pharmacotherapy of osteoporosis].

Osteoporosis with increased risk of bone fracture is a disabling syndrome that naturally occurs as long as one ages and moves on two legs. Recent progress in bone cell biology has shed light on the mechanisms underlying the anti-osteoporotic properties of drugs that have been in use for a long time, providing a fresh stage for novel pharmacotherapies. In addition, large scale clinical trials developed in the past decade appear not only to rationalize the clinical utilities of these drugs but also to provide new concepts for the development of new therapeutic modalities.

[Anti-osteopenic effect of taurine: possible involvement of activated MEK-ERK-Cbfa1 signaling].

Previously we first noted that taurine (TR) has anti-osteopenic effect on low Ca diet-induced osteopenia in rats (1). Employing osteoblastic MC3T3-E1 cells, the mechanism of the anti-osteopenic effect was explored in vitro. TR (1 mM) was found to promote mineralization of extracellular matrices, without affecting alkaline phosphataase activity.

New signaling pathway for parathyroid hormone and cyclic AMP action on extracellular-regulated kinase and cell proliferation in bone cells. Checkpoint of modulation by cyclic AMP.

cAMP signaling, activated by extracellular stimuli such as parathyroid hormone, has cell type-specific effects important for cellular proliferation and differentiation in bone cells. Recent evidence of a second enzyme target for cAMP suggests divergent effects on extracellular-regulated kinase (ERK) activity depending on Epac/Rap1/B-Raf signaling. We investigated the molecular mechanism of the dual functionality of cAMP on cell proliferation in clonal bone cell types.