The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts.

The cytoskeletal organization of osteoclasts is required for bone resorption. Binding of dynamin with guanosine triphosphate (GTP) was previously suggested to be required for the organization of the actin cytoskeleton. However, the role of the GTPase activity of dynamin in the organization of the actin cytoskeleton as well as in the bone-resorbing activity of osteoclasts remains unclear. This study investigated the effects of dynasore, an inhibitor of the GTPase activity of dynamin, on the bone-resorbing activity of and actin ring formation in mouse osteoclasts in vitro and in vivo. Dynasore inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation and rapidly disrupting actin rings in osteoclasts. A time-lapse image analysis showed that dynasore shrank actin rings in osteoclasts within 30 min. The intraperitoneal administration of dynasore inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced trabecular bone loss in mouse femurs. These in vitro and in vivo results suggest that the GTPase activity of dynamin is critical for the bone-resorbing activity of osteoclasts and that dynasore is a seed for the development of novel anti-resorbing agents.

Wnt16 regulates osteoclast differentiation in conjunction with Wnt5a.

The canonical Wnt/ß-catenin signaling pathway in osteoblast-lineage cells inhibits osteoclastogenesis through the expression of osteoprotegerin (Opg), a decoy receptor of receptor activator of Nf-κb (Rank) ligands. Wnt5a, a typical non-canonical Wnt ligand, enhances the expression of Rank in osteoclast precursors, which, in turn, promotes the Rank ligand (Rankl)-induced formation of osteoclasts. In contrast, Wnt16 and Wnt4 have been shown to inhibit the Rankl-induced formation of osteoclasts through non-canonical Wnt signals. However, the relationships among these Wnt ligands in osteoclastogenesis remained to be elucidated. We herein showed that Wnt16, but not Wnt4, inhibited the Rankl-induced osteoclastogenesis in bone marrow-derived macrophage (BMM) cultures. Wnt3a and Wnt4 inhibited the 1α,25-dihydroxy vitamin D3 (1,25D3)-induced osteoclastogenesis in co-cultures prepared from wild-type mice, but not in those from Opg(-/-) nice. Wnt16 inhibited the 1,25D3-induced formation of osteoclasts in both wild-type and Opg(-/-) co-cultures. Wnt16, Wnt4, and Wnt3a failed to inhibit the pit-forming activity of osteoclasts. Wnt16 failed to inhibit the Wnt5a-induced expression of Rank in osteoclast precursors. In contrast, Wnt5a abrogated the inhibitory effects of Wnt16 on Rankl-induced osteoclastogenesis. These results suggested that Wnt16 inhibited osteoclastogenesis, but not the function of osteoclasts and that Wnt16, an inhibitory Wnt ligand for osteoclastogenesis, regulates bone resorption in conjunction with Wnt5a.

The crown angulations and inclinations in Dravidian population with normal occlusion.

BACKGROUND: There has always been a constant search for the definition of idealistic and realistic orthodontic treatment goals for different ethnic groups around the world. This study was hence devised to study the mesio-distal angulations and labio-lingual inclinations of the clinical crowns in Dravidian population with pleasing profiles and non-orthodontic normal occlusion. MATERIALS AND METHODS: Forty dental casts from a Dravidian sample (21.5 years) with Class I canine and molar relation; normal maxillo-mandibular relationship; well-aligned arches; with no dental anomaly, restorations or attrition; no history of previous orthodontic treatment, and exhibiting normal growth were studied. A custom-made tip-torque device was used to measure the crown angulations and inclinations. The arithmetic mean and standard deviations for each tooth type were compared with those of Andrew's Caucasian norms using Student's 't' test. RESULTS: The study group exhibited statistically significant decrease in crown angulation (mesial tip) and increased labial crown torque in both upper and lower anteriors. The lower anteriors exhibited distal crown tip while the posteriors were significantly tipped more mesially. All the posteriors demonstrated increased lingual crown torque. CONCLUSION: Tip and torque modifications are suggested for the fine finishing and easy retention of occlusion in Dravidians while using straight wire appliance.