Black bear parathyroid hormone and methods of using black bear parathyroid hormone

Black bear parathyroid hormone (PTH) and functional fragments thereof are provided. Also provided are methods of using black bear PTH and functional fragments for increasing cAMP in a bone-forming cell; reducing apoptosis in a bone-forming cell; decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell; increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell; enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a subject; also provided are antibodies directed against black bear parathyroid hormone (PTH) and functional fragments thereof.https://digitalcommons.mtu.edu/patents/1002/thumbnail.jp

Cell culture method and apparatus for mechanically stimulating cells

A cell culture assembly and a method for culturing cells that provide mechanical stimulation to cells. The cell culture assembly can include a flow chamber positioned in a fluid path and a support comprising cells positioned within the flow chamber to expose the cells to the fluid path. The cell culture assembly can further include a means for producing a steady flow of fluid in the fluid path, and a means for producing an oscillatory flow of fluid in the fluid path simultaneously with producing the steady flow of fluid in the fluid path to mechanically stimulate the cells. The method can include transporting fluid in the fluid path at a substantially steady flow rate, and transporting fluid in the fluid path at a substantially oscillatory flow rate simultaneously with transporting fluid in the fluid path at a substantially steady flow rate.https://digitalcommons.mtu.edu/patents/1023/thumbnail.jp

Methods of using black bear parathyroid hormone

Black bear parathyroid hormone (PTH) and functional fragments thereof are provided. Also provided are methods of using black bear PTH and functional fragments for increasing cAMP in a bone-forming cell; reducing apoptosis in a boneforming cell; decreasing the ratio of expression levels of Bax protein to Bcl-2 protein in a bone-forming cell; increasing the expression level of one or more of a bone matrix protein, a transcriptional activator, or a transcriptional regulator in a bone-forming cell; enhancing bone mineral density, increasing bone mass, decreasing bone loss, or reducing the incidence of bone fractures, or any combination thereof, in a subject; also provided are antibodies directed against black bear parathyroid hormone (PTH) and functional fragments thereof.https://digitalcommons.mtu.edu/patents/1018/thumbnail.jp

Star formation and UV colors of the brightest Cluster Galaxies in the representative XMM-Newton Cluster Structure Survey

We present UV broadband photometry and optical emission-line measurements for a sample of 32 Brightest Cluster Galaxies (BCGs) in clusters of the Representative XMM-Newton Cluster Structure Survey (REXCESS) with z = 0.06-0.18. The REXCESS clusters, chosen to study scaling relations in clusters of galaxies, have X-ray measurements of high quality. The trends of star formation and BCG colors with BCG and host properties can be investigated with this sample. The UV photometry comes from the XMM Optical Monitor, supplemented by existing archival GALEX photometry. We detected H\alpha and forbidden line emission in 7 (22%) of these BCGs, in optical spectra. All of the emission-line BCGs occupy clusters classified as cool cores, for an emission-line incidence rate of 70% for BCGs in cool core clusters. Significant correlations between the H\alpha equivalent widths, excess UV production in the BCG, and the presence of dense, X-ray bright intracluster gas with a short cooling time are seen, including the fact that all of the H\alpha emitters inhabit systems with short central cooling times and high central ICM densities. Estimates of the star formation rates based on H\alpha and UV excesses are consistent with each other in these 7 systems, ranging from 0.1-8 solar masses per year. The incidence of emission-line BCGs in the REXCESS sample is intermediate, somewhat lower than in other X-ray selected samples (-35%), and somewhat higher than but statistically consistent with optically selected, slightly lower redshift BCG samples (-10-15%). The UV-optical colors (UVW1-R-4.7\pm0.3) of REXCESS BCGs without strong optical emission lines are consistent with those predicted from templates and observations of ellipticals dominated by old stellar populations. We see no trend in UV-optical colors with optical luminosity, R-K color, X-ray temperature, redshift, or offset between X-ray centroid and X-ray peak ().Comment: 19 pages, 18 figures, 6 tables. Submitted, with minor revisions, to ApJ

Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and Preservation of Bone Architecture and Strength in Hibernating Marmots

Periods of physical inactivity increase bone resorption and cause bone loss and increased fracture risk. However, hibernating bears, marmots, and woodchucks maintain bone structure and strength, despite being physically inactive for prolonged periods annually. We tested the hypothesis that bone turnover rates would decrease and bone structural and mechanical properties would be preserved in hibernating marmots (Marmota flaviventris). Femurs and tibias were collected from marmots during hibernation and in the summer following hibernation. Bone remodeling was significantly altered in cortical and trabecular bone during hibernation with suppressed formation and no change in resorption, unlike the increased bone resorption that occurs during disuse in humans and other animals. Trabecular bone architecture and cortical bone geometrical and mechanical properties were not different between hibernating and active marmots, but bone marrow adiposity was significantly greater in hibernators. Of the 506 proteins identified in marmot bone, 40 were significantly different in abundance between active and hibernating marmots. Monoaglycerol lipase, which plays an important role in fatty acid metabolism and the endocannabinoid system, was 98-fold higher in hibernating marmots compared with summer marmots and may play a role in regulating the changes in bone and fat metabolism that occur during hibernation

Osteoblastic cells have refractory periods for fluid-flow-induced intracellular calcium oscillations for short bouts of flow and display multiple low-magnitude oscillations during long-term flow

Partitioning a daily mechanical stimulus into discrete loading bouts enhances bone formation in rat tibiae (J. Bone Mineral Res. 15(8) (2000) 1596). We hypothesized that a refractory period exists in primary rat osteoblastic cells, during which fluid-flow-induced [Ca2+]i oscillations are insensitive to additional short bouts (2min) of fluid flow. Because the frequency of [Ca2+]i oscillations is believed to be important for regulating cellular activity and long-term fluid flow alters gene expression in bone cells, we also hypothesized that long-term (15min) oscillating fluid flow produces multiple [Ca2+]i oscillations in osteoblastic cells. Primary osteoblastic cells from rat long bones were exposed to 2min of oscillating fluid flow that produced shear stresses of 2Pa at 2Hz. After a rest period of 5, 30, 60, 300, 600, 900, 1800, or 2700s, the cells were exposed to a second 2-min bout of flow. A 600s rest period was required to recover the percentage of cells responding to fluid flow and a 900s rest period was required to recover the [Ca2+]i oscillation magnitude. The magnitude and shape of the two [Ca2+]i oscillations were strikingly similar for individual cells after a 900s rest period. During 15min of continuous oscillating flow, some individual cells displayed between 1 and 9 oscillations subsequent to the initial [Ca2+]i oscillation. However, only 54% of the cells that responded initially displayed subsequent [Ca2+]i oscillations during long-term flow and the magnitude of the subsequent oscillations was only 28% of the initial response. © 2002 Elsevier Science Ltd. All rights reserved

Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent

Bone adaptation to mechanical loading is dependent on age and the frequency and magnitude of loading. It is believed that load-induced fiuid flow in the porous spaces of bone is an important signal that influences bone cell metabolism and bone adaptation. We used fluid fiow-induced shear stress as a mechanical stimulus to study intracellular calcium (Cai2+) signaling in rat osteoblastic cells (ROB) isolated from young, mature, and old animals. Fluid fiow produced higher magnitude and more abundant [Ca2+]i oscillations than spontaneous oscillations, suggesting that flow-induced Cai2+ signaling encodes a different cellular message than spontaneous oscillations. ROB from old rats showed less basal [Ca2+]i activity and were less responsive to fluid flow. Cells were more responsive to 0.2 Hz than to 1 or 2 Hz and to 2 Pa than to 1 Pa. These data suggest that the frequency and magnitude of mechanical loading may be encoded by the percentage of cells displaying [Ca2+]i oscillations but that the ability to transduce this information may be altered with age

Microdamage in bone: Implications for fracture, repair, remodeling, and adaptation

Fatigue microdamage accumulates in bone as a result of physiological loading. The damage is often manifested as microcracks, which are typically 50-100 μm long. These types of cracks develop in the interstitial bone and frequently abut osteon cement lines. In vitro experimentation has shown that an accumulation of fatigue damage reduces the material properties of bone (e.g., elastic modulus). An accumulation of fatigue damage has been implicated in the etiology of stress fractures and fragility fractures. However, bone has a remarkable ability to detect and repair fatigue microdamage. This article reviews the experimental techniques for identifying and quantifying different types of microdamage in bone, the density of in vivo microcracks at different skeletal locations, the effect of microdamage on bone material properties, the role of microdamage in bone fracture, and the biological mechanisms for the detection and repair of fatigue microdamage. © 2006 by Begell House, Inc

Bending properties, porosity, and ash fraction of black bear (Ursus americanus) cortical bone are not compromised with aging despite annual periods of disuse

In many species, including humans, disuse causes an imbalance in bone remodeling that leads to increased bone porosity as a result of increased bone resorption and decreased bone formation. However, black bears (Ursus americanus) may not develop disuse osteopenia, to the extent that other animals do, during long periods of disuse (i.e. hibernation) because they maintain osteoblastic bone formation during hibernation, even though bone resorption is increased during hibernation. Black bears may also have a mechanism to rapidly and completely recover the bone lost (by increased resorption during hibernation) during their remobilization period. Our findings suggest that cortical bone bending strength (211-328MPa), bending modulus (16.0-29.5MPa), fracture energy (0.0118-0.0205Jmm-2), porosity (2.3-7.1%), and ash fraction (0.638-0.672) are not compromised with age in black bears, despite annual periods of disuse. In fact, the ultimate strength (p=0.01), modulus (p=0.04), and ash fraction (p=0.03) of cortical bone were shown to significantly increase with age (2-14 yrs). Female bears give birth and nurse during hibernation; however, we found no significant (p\u3e 0.16) differences between male and female bone properties. Other animals require remobilization periods 2-3 times longer than the immobilization period to recover the bone lost during disuse. Our findings support the idea that black bears, which hibernate 5-7 months annually, have evolved a biological mechanism to mitigate the adverse effects of disuse on bone porosity and mechanical behavior. © 2004 Elsevier Ltd. All rights reserved

Serum markers of bone metabolism show bone loss in hibernating bears

Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals