Delivery of Ad-BMP-2 or Ad-BMP-6 via direct injection supported cartilage and subchondral bone regeneration but was insufficient to provide long-term quality osteochondral repair.

The functions of parathyroid hormone-related protein (PTHrP) on morphogenesis, cell proliferation, apoptosis, and calcium homeostasis have been attributed to its N terminus. Evidence suggests that many of these effects are not mediated by the N terminus but by the midregion, a nuclear localization sequence (NLS), and C terminus of the protein. A knock-in mouse lacking the midregion, NLS, and C terminus of PTHrP (Pthrp(Delta/Delta)) was developed. Pthrp(Delta/Delta) mice had craniofacial dysplasia, chondrodysplasia, and kyphosis, with most mice dying by d 5 of age. In bone, there were fewer chondrocytes and osteoblasts per area, bone mass was decreased, and the marrow was less cellular, with erythroid hypoplasia. Cellular proliferation was impaired, and apoptosis was increased. Runx2, Ocn, Sox9, Crtl1, beta-catenin, Runx1, ephrin B2, cyclin D1, and Gata1 were underexpressed while P16/Ink4a, P21, GSK-3beta, Il-6, Ffg3, and Ihh were overexpressed. Mammary gland development was aberrant, and energy metabolism was deregulated. These results establish that the midregion, NLS, and C terminus of PTHrP are crucial for the commitment of osteogenic and hematopoietic precursors to their lineages, and for survival, and many of the effects of PTHrP on development are not mediated by its N terminus. The down-regulation of Runx1, Runx2, and Sox9 indicates that PTHrP is a modulator of transcriptional activation during stem cell commitment.

Animals sample sensory stimuli for longer periods when they must perform difficult discrimination tasks, implying that the brain's ability to represent stimuli improves as a function of time. Though it is true in other senses, few studies have examined whether increasing sampling time improves olfactory discrimination. In the experiments reported here, we controlled odor sampling time with the goal of testing whether odor concentration affected a honeybee's ability to learn, recognize, and discriminate odors. We observed that increasing sampling time during conditioning and testing improved a honeybee's ability to learn, recognize, and differentiate low concentration (0.0002M) odors. For intermediate (0.02M) concentration odors, both acquisition and recognition improved when stimulus duration was longer, but discrimination was unaffected. Having longer to sample a high concentration (2.0M) stimulus also improved acquisition, but it did not affect the ability to recognize or differentiate odors. Differences in the time taken to respond to the conditioned and novel odors during the test period depended upon the difficulty of the discrimination task. Our results suggest that the sensory coding of molecular identity takes longer for low concentration odors.