Long time exposure to soy/isoflavone-rich diet enhances testicular and prostate health in Long-Evans rats

Authors

Crystal Blake, Trevor Hansen, Trent C. Simmons, Edwin D. Lephart

Abstract

Soy isoflavone consumption appears to be beneficial for several health parameters. We report the influence of (lifelong exposure to) a high soy/isoflavone (High-Iso) compared to a low soy/isoflavone (Low-Iso) diet on body weight (BW), white adipose tissue (WAT) deposition, prostate weight (PW), testicular weight (TW), and testosterone levels in young adult male Long-Evans rats. WAT deposition and the WAT/BW ratios were significantly less in High-Iso vs. the Low-Iso fed animals. TW and TW/BW ratios were significantly greater in High-Iso vs. Low-Iso fed animals. Sertoli cell area, seminiferous tubule lumens and seminiferous tubule areas were significantly greater in High-Iso vs. Low-Iso animals. These data suggest that consumption of a soy diet high in isoflavone/polyphenolic molecules from conception appear to be beneficial in decreasing PW and WAT deposition while increasing TW, Sertoli cell area and seminiferous tubule volume.

Link to Article

http://dx.doi.org/10.1016/j.jff.2013.04.009

Expression of C-fos in hilar mossy cells of the dentate gyrus in vivo

Authors

Aine M. Duffy, Michael J. Schaner, Jeannie Chin, Helen E. Scharfman

Abstract

Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent—they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. Therefore, adult male rats were perfused shortly after removal from their home cage and transfer to the laboratory. Remarkably, most c-fos immunoreactivity (ir) was in the hilus, especially temporal hippocampus. C-fos-ir hilar cells co-expressed GluR2/3, suggesting that they were MCs. C-fos-ir MCs were robust even when the animal was habituated to the investigator and laboratory where they were euthanized. However, c-fos-ir in dorsal MCs was reduced under these circumstances, suggesting that ventral and dorsal MCs are functionally distinct. Interestingly, there was an inverse relationship between MC and GC layer c-fos expression, with little c-fos expression in the GC layer in ventral sections where MC expression was strong, and the opposite in dorsal hippocampus. The results support the hypothesis that a subset of hilar MCs are spontaneously active in vivo and provide other DG neurons with tonic depolarizing input.

Link to Article

http://dx.doi.org/10.1002/hipo.22138

Heat and radiofrequency plasma glow discharge pretreatment of a titanium alloy promote bone formation and osseointegration

Authors

Daniel E. MacDonald, Bruce E. Rapuano, Parth Vyas, Joseph M. Lane, Kathleen Meyers, Timothy Wright

Abstract

Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600 °C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r2 = 0.87 − 0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3 to 5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material.

Link to Article

http://dx.doi.org/10.1002/jcb.24585

Scaling of Haversian canal surface area to secondary osteon bone volume in ribs and limb bones

Authors

John G. Skedros, Alex N. Knight, Gunnar C. Clark, Christian M. Crowder, Victoria M. Dominguez, Shijing Qiu, Dawn M. Mulhern, Seth W. Donahue, Björn Busse, Brannon I. Hulsey, Marco Zedda, Scott M. Sorenson

Abstract

Studies of secondary osteons in ribs have provided a great deal of what is known about remodeling dynamics. Compared with limb bones, ribs are metabolically more active and sensitive to hormonal changes, and receive frequent low-strain loading. Optimization for calcium exchange in rib osteons might be achieved without incurring a significant reduction in safety factor by disproportionally increasing central canal size with increased osteon size (positive allometry). By contrast, greater mechanical loads on limb bones might favor reducing deleterious consequences of intracortical porosity by decreasing osteon canal size with increased osteon size (negative allometry). Evidence of this metabolic/mechanical dichotomy between ribs and limb bones was sought by examining relationships between Haversian canal surface area (BS, osteon Haversian canal perimeter, HC.Pm) and bone volume (BV, osteonal wall area, B.Ar) in a broad size range of mature (quiescent) osteons from adult human limb bones and ribs (modern and medieval) and various adult and subadult non-human limb bones and ribs. Reduced major axis (RMA) and least-squares (LS) regressions of HC.Pm/B.Ar data show that rib and limb osteons cannot be distinguished by dimensional allometry of these parameters. Although four of the five rib groups showed positive allometry in terms of the RMA slopes, nearly 50% of the adult limb bone groups also showed positive allometry when negative allometry was expected. Consequently, our results fail to provide clear evidence that BS/BV scaling reflects a rib versus limb bone dichotomy whereby calcium exchange might be preferentially enhanced in rib osteons.

Link to Article

http://dx.doi.org/10.1002/ajpa.22270

Positive regulation of osteogenesis by bile acid through FXR

Authors

Sun Wook Cho MD, Jee Hyun An MD, Hyojung Park PhD, Jae-Yeon Yang MS, Hyung Jin Choi MD, Sang Wan Kim MD, Young Joo Park MD, Seong Yeon Kim MD, Mijung Yim PhD, Wook-Young Baek PhD, Jung-Eun Kim MD, Chan Soo Shin MD

Abstract

Farnesoid X receptor (FXR) is a nuclear receptor, which functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR−/−) in vivo resulted in a significant reduction in bone mineral density by 4.3∼6.6% in mice 8 to 20 weeks of age compared with FXR+/+ mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, TRACP staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR−/− mice compared with FXR+/+ mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR−/− mice compared with FXR+/+ mice in concert with a significant reduction in Col1a1, ALP, and Runx2 gene expressions. Cultures of bone marrow derived macrophages from FXR−/− mice exhibited an increased number of osteoclast formations and protein expression of NFATc1. In female FXR−/− mice, although BMD was not significantly different from that in FXR+/+ mice, bone loss was accelerated after an ovariectomy compared with FXR+/+ mice. In vitro, activation of FXR by bile acids (CDCA or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced ERK and β-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol diet (1%) marginally prevented OVX-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways, i.e. bone formation and resorption.

Link to Article

http://dx.doi.org/10.1002/jbmr.1961

E-selectin ligand 1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment

Authors

Tao Yang, Ingo Grafe, Yangjin Bae, Shan Chen, Yuqing Chen, Terry K. Bertin, Ming-Ming Jiang, Catherine G. Ambrose, and Brendan Lee

Abstract

TGF-β is abundantly produced in the skeletal system and plays a crucial role in skeletal homeostasis. E-selectin ligand-1 (ESL-1), a Golgi apparatus-localized protein, acts as a negative regulator of TGF-β bioavailability by attenuating maturation of pro–TGF-β during cartilage homeostasis. However, whether regulation of intracellular TGF-β maturation by ESL-1 is also crucial during bone homeostasis has not been well defined. Here, we show that Esl-1−/− mice exhibit a severe osteopenia with elevated bone resorption and decreased bone mineralization. In primary culture, Esl-1−/− osteoclast progenitors show no difference in osteoclastogenesis. However, Esl-1−/− osteoblasts show delayed differentiation and mineralization and stimulate osteoclastogenesis more potently in the osteoblast–osteoclast coculture, suggesting that ESL-1 primarily acts in osteoblasts to regulate bone homeostasis. In addition, Esl-1−/− calvaria exhibit an elevated mature TGF-β/pro–TGF-β ratio, with increased expression of TGF-β downstream targets (plasminogen activator inhibitor-1, parathyroid hormone-related peptide, connective tissue growth factor, and matrix metallopeptidase 13, etc.) and a key regulator of osteoclastogenesis (receptor activator of nuclear factor κB ligand). Moreover, in vivo treatment with 1D11, a pan–TGF-β antibody, significantly improved the low bone mass of Esl-1−/− mice, suggesting that elevated TGF-β signaling is the major cause of osteopenia in Esl-1−/− mice. In summary, our study identifies ESL-1 as an important regulator of bone remodeling and demonstrates that the modulation of TGF-β maturation is pivotal in the maintenance of a homeostatic bone microenvironment and for proper osteoblast–osteoclast coupling.

Link to Article

http://dx.doi.org/10.1073/pnas.1219748110