bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo
Authors: Roelofs Anke J , Coxon Fraser P , Ebetino Frank H , Lundy Mark W , Henneman Zachary J , Nancollas George H , Sun Shuting , Blazewska Katarzyna M , Bala Joy Lynn F , Kashemirov Boris A , Khalid Aysha B , McKenna Charles E , Rogers Michael J 
Published: October 2009

Abstract
Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647–labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research
Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function
Authors: Bentmann Anke , Kawelke Nina , Moss David , Zentgraf Hanswalter , Bala Yohann , Berger Irina , Gasser Juerg A , Nakchbandi Inaam A 
Published: October 2009

Abstract
The bone matrix is composed mostly of collagen, but the initial and continuous presence of fibronectin was found to be crucial for collagen matrix integrity in vitro. It has been assumed that osteoblasts produce the fibronectin required for bone matrix formation. Using transgenic mice, we conditionally deleted fibronectin in the osteoblasts and in the liver using the cre-loxP system. We also used mice with mutated fibronectin and conditionally deleted β1-integrin in osteoblasts to identify the receptor involved in fibronectin effects on osteoblasts. Conditional deletion of fibronectin in the differentiating osteoblasts [using the 2.3 kb collagen-α1(I) promoter] failed to show a decrease in fibronectin amount in the bone matrix despite evidence of successful deletion. Using these mice we established that osteoblast-derived fibronectin solely affects osteoblast function. This effect was not mediated by integrins that bind to the RGD motif. Conditional deletion of fibronectin in the liver showed a marked decrease in fibronectin content in the matrix associated with decreased mineral-to-matrix ratio and changed biomechanical properties but had no effect on osteoblasts or osteoclasts. In conclusion, osteoblast fibronectin affects osteoblasts function. This does not seem to be mediated by the RGD motif on fibronectin. In contrast, liver-derived fibronectin affects bone matrix properties without affecting osteoblast or osteoclast function. A novel role for liver-derived circulating fibronectin thus was defined and delineated from that of locally produced fibronectin. © 2010 American Society for Bone and Mineral Research
Knee and hip radiographic osteoarthritis predict total hip bone loss in older adults: A prospective study
Authors: Ding Changhai , Cicuttini Flavia , Boon Catrina , Boon Pip , Srikanth Velandai , Cooley Helen , Jones Graeme 
Published: October 2009

Abstract
The relationship between osteoarthritis (OA) and osteoporosis remains controversial. This study was designed to determine the association between hip and knee radiographic OA and change in total hip bone mineral density (BMD) over 2.6 years. A total of 867 population-based randomly selected subjects (mean age 62 years, range 51 to 80 years, and 49% female) were included. Hip and knee joint space narrowing (JSN, 0 to 3) and osteophytes (0 to 3) in both lower limbs was assessed using Altman's atlas. Total hip BMD was measured by dual-energy X-ray absorptiometry (DXA). We found that radiographic OA (score of JSN or osteophytes &gt; 0) was common in this sample (hip 45%, knee 68%). In multivariable analyses, percentage change in total hip BMD per year was predicted by right and left hip axial JSN (β = –0.25% and –0.29% per grade, respectively, both p &lt; .05), right hip superior femoral osteophytes (grades 2 and 3 versus 0: β = –1.60, p &lt; .05), combined right and left knee tibiofemoral JSN (β = –0.06 per grade from grades 0 to 12, p &lt; .05), and osteophytes (β = –0.06 per grade from grades 0 to 14, p &lt; .05) independent of each other and joint pain. In conclusion, older subjects with radiographic hip and knee OA have higher total hip bone loss over 2.6 years regardless of symptoms, suggesting that consideration should be given to the monitoring of bone mass in these subjects. © 2010 American Society for Bone and Mineral Research.
A functional polymorphism in MMP1 could influence osteomyelitis development
Authors: Montes Angel Hugo , Valle-Garay Eulalia , Alvarez Victoria , Pevida Marta , García Pérez Eva , Paz Jose , Meana Alvaro , Asensi Victor 
Published: October 2009

Abstract
Osteomyelitis (OM) is a bone infection characterized by necrosis and new formation of bone. Because matrix metalloproteases (MMPs) play an important role in bone extracellular matrix remodeling, we investigated the role of some MMP polymorphisms in OM patients. A total of 118 OM patients and 300 blood donors were genotyped for the polymorphisms of MMP1 (−1607 1G/2G) and MMP13 (−77A/G). Levels of MMPs (−1, −2, −3, −8, -9, −10, and −13) and tissue inhibitors of metaloproteases (TIMP-1, -2, and -4) in serum and in human osteoblasts obtained from OM biopsies also were determined. The MMP1 (–1607 2G/2G) genotype was significantly more frequent among OM patients compared with controls [65.3% versus 33.7%, χ2 = 26.85, odds ratio (OR) = 3.24, 95% confidence interval (CI) 2.03–5.2, p &lt; .0001]. The MMP1 2G allele also was more frequent in OM patients (73.3% versus 57.2%, χ2 = 37.76, OR = 2.75, 95% CI 1.96–3.85, p &lt; .0001). Carriers of the 2G allele had significantly higher osteoblast MMP1 mRNA and MMP-1 serum levels than noncarriers (p &lt; .04). Interleukin 1α (IL-1α) increased MMP-1 and -13 protein secretion and Ets1 mRNA expression by OM patients' osteoblasts. No association of the MMP13 (–77 A/G) polymorphism with OM was observed. The MMP1 (–1607 1G/2G) polymorphism might contribute to OM pathogenesis. This could be due to increased expression of MMP-1 by osteoblasts and is regulated by IL-1α. © 2010 American Society for Bone and Mineral Research
Association with replication between estrogen-related receptor γ (ESRRγ) Polymorphisms and bone phenotypes in women of European ancestry
Authors: Elfassihi Latifa , Giroux Sylvie , Bureau Alexandre , Laflamme Nathalie , Cole David EC , Rousseau François 
Published: October 2009

Abstract
Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor γ (ESRRγ) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRγ sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRγ in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research
Growth hormone regulates the balance between bone formation and bone marrow adiposity
Authors: Menagh Philip J , Turner Russell T , Jump Donald B , Wong Carmen P , Lowry Malcolm B , Yakar Shoshana , Rosen Clifford J , Iwaniec Urszula T 
Published: October 2009

Abstract
Cancellous bone decreases and bone marrow fat content increases with age. Osteoblasts and adipocytes are derived from a common precursor, and growth hormone (GH), a key hormone in integration of energy metabolism, regulates the differentiation and function of both cell lineages. Since an age-related decline in GH is associated with bone loss, we investigated the relationship between GH and bone marrow adiposity in hypophysectomized (HYPOX) rats and in mice with defects in GH signaling. HYPOX dramatically reduced body weight gain, bone growth and mineralizing perimeter, serum insulin-like growth factor 1 (IGF-1) levels, and mRNA levels for IGF-1 in liver and bone. Despite reduced body mass and adipocyte precursor pool size, HYPOX resulted in a dramatic increase in bone lipid levels, as reflected by increased bone marrow adiposity and bone triglyceride and cholesterol content. GH replacement normalized bone marrow adiposity and precursor pool size, as well as mineralizing perimeter in HYPOX rats. In contrast, 17β -estradiol, IGF-1, thyroxine, and cortisone were ineffective. Parathyroid hormone (PTH) reversed the inhibitory effects of HYPOX on mineralizing perimeter but had no effect on adiposity. Finally, bone marrow adiposity was increased in mice deficient in GH and IGF-1 but not in mice deficient in serum IGF-1. Taken together, our findings indicate that the reciprocal changes in bone and fat mass in GH signaling-deficient rodents are not directly coupled with one another. Rather, GH enhances adipocyte as well as osteoblast precursor pool size. However, GH increases osteoblast differentiation while suppressing bone marrow lipid accumulation. © 2010 American Society for Bone and Mineral Research
Microdamage repair and remodeling requires mechanical loading
Authors: Waldorff Erik I , Christenson Katya B , Cooney Laura A , Goldstein Steven A 
Published: October 2009

Abstract
Bone remodeling is necessary to avoid microdamage accumulation, which could lead to whole-bone failure. Previous studies have shown that this bone-repair mechanism is triggered by osteocyte apoptosis. Through the use of a rodent hindlimb suspension model and tibial four-point bending model, the effects of disuse on microdamage remodeling was examined. At day 0, male rats were assigned to one of three groups: weight bearing (WB), hindlimb suspension (HS), or hindlimb suspension with daily intermittent weight bearing following damage-inducing loading (HW). Within each group, the rats were further divided into subgroups corresponding to three sacrifice time points [day 14 (WB and HS only), day 18, or day 35]. At day 14, animals were anesthetized, and their left tibiae underwent cyclic four-point bending to produce fatigue-induced microdamage. At sacrifice, the tibiae were examined using 3D micro-computed tomography (µCT), flow cytometry, and histologic and immunohistochemical stains. The results indicate that only the WB and HW groups had a significant increase in intracortical TRAP-positive resorption pits following damage induction, which was paralleled by a significant decrease in microdamage over time in combination with a shift in the osteoclast lineage owing to a decrease in monocytes. These results demonstrate that osteocyte apoptosis may be insufficient for repair of microdamage without the stimulation provided through physiologic loading. In addition, this potentially could have clinical implications for the current therapeutic paradigm for treating stress fractures, where extended non-weight bearing is employed. © 2010 American Society for Bone and Mineral Research
Identifying a molecular phenotype for bone marrow stromal cells with in vivo bone-forming capacity
Authors: Larsen Kenneth H , Frederiksen Casper M , Burns Jorge S , Abdallah Basem M , Kassem Moustapha 
Published: October 2009

Abstract
The ability of bone marrow stromal cells (BMSCs) to differentiate into osteoblasts is being exploited in cell-based therapy for repair of bone defects. However, the phenotype of ex vivo cultured BMSCs predicting their bone-forming capacity is not known. Thus we employed DNA microarrays comparing two human bone marrow stromal cell (hBMSC) populations: One is capable of in vivo heterotopic bone formation (hBMSC-TERT+Bone), and the other is not (hBMSC-TERT–Bone). Compared with hBMSC-TERT–Bone, the hBMSC-TERT+Bone cells had an increased overrepresentation of extracellular matrix genes (17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor–binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT–Bone cells expressed a larger number of immune-response-related genes (26% versus 8%). In order to test for the predictive value of these markers, we studied the correlation between their expression levels in six different hBMSC-derived clones and the ability to form bone in vivo. We found a significant correlation for decorin, lysyl oxidase-like 4, natriuretic peptide receptor C, and tetranectin. No significant positive correlation was found for canonical osteoblastic markers Runx2, alkaline phosphatase, collagen type I, osteopontin, and bone sialoprotein. Prospective isolation of four additional hBMSC clones based on their expression levels of the molecular markers correlated with their in vivo bone-formation ability. In conclusion, our data suggest an in vitro molecular signature predictive for hBMSCs' in vivo bone-formation ability. Identifying more of these predictive markers would be very useful in the quality control of osteoblastic cells before use in therapy. © 2010 American Society for Bone and Mineral Research
Parathyroid hormone induction of cyclooxygenase-2 in murine osteoblasts: Role of the calcium-calcineurin-NFAT pathway
Authors: Huang Hechang , Chikazu Daichi , Voznesensky Olga S , Herschman Harvey R , Kream Barbara E , Drissi Hicham , Pilbeam Carol C 
Published: October 2009

Abstract
Murine MC3T3-E1 and MC-4 cells were stably transfected with −371/+70 bp of the murine cyclooxygenase-2 (COX-2) promoter fused to a luciferase reporter (Pluc371) or with Pluc371 carrying site-directed mutations. Mutations were made in (1) the cAMP response element (CRE) at −57/−52 bp, (2) the activating protein-1 (AP-1)–binding site at −69/−63 bp, (3) the nuclear factor of activated T-cells (NFAT)–binding site at −77/−73 bp, and (4) both the AP-1 and NFAT sites, which comprise a composite consensus sequence for NFAT/AP-1. Single mutation of CRE, AP-1, or NFAT sites decreased parathyroid hormone (PTH)–stimulated COX-2 promoter activity 40% to 60%, whereas joint mutation of NFAT and AP-1 abrogated the induction. On electrophoretic mobility shift analysis, PTH stimulated binding of phosphorylated CREB to an oligonucleotide spanning the CRE and binding of NFATc1, c-Fos, and c-Jun to an oligonucleotide spanning the NFAT/AP-1 composite site. Mutation of the NFAT site was less effective than mutation of the AP-1 site in competing binding to the composite element, suggesting that cooperative interactions of NFATc1 and AP-1 are more dependent on NFAT than on AP-1. Both PTH and forskolin, an activator of adenylyl cyclase, stimulated NFATc1 nuclear translocation. PTH- and forskolin-stimulated COX-2 promoter activity was inhibited 56% to 80% by calcium chelation or calcineurin inhibitors and 60% to 98% by protein kinase A (PKA) inhibitors. These results indicate an important role for the calcium-calcineurin-NFAT signaling pathway in the PTH induction of COX-2 and suggest that cross-talk between the cAMP/PKA pathway and the calcium-calcineurin-NFAT pathway may play a role in other functions of PTH in osteoblasts. © 2010 American Society for Bone and Mineral Research
Fishing Mortality in North Carolina's Southern Flounder Fishery: Direct Estimates of Instantaneous Fishing Mortality from a Tag Return Experiment
Authors: Smith William E. , Scharf Frederick S. , Hightower Joseph E. 
Published: October 2009

Abstract
Estimation of harvest rates is often a critical component of fishery stock assessment and management. These assessments are often based on catch-at-age data sets generated over many years, but estimates of instantaneous fishing mortality (F) can also be obtained from a shorter-term tag return study. We conducted a 2-year tag return experiment to generate direct estimates of F for southern flounder Paralichthys lethostigma in a North Carolina estuary. The southern flounder supports lucrative commercial and recreational fisheries within the state and has experienced heavy fishing pressure for more than a decade. During 2005 and 2006, fish were captured and tagged with the assistance of commercial harvesters in the New River estuary. Tag returns were used to generate monthly estimates of F, which demonstrated a clear seasonal pattern that was consistent between years. Several important assumptions of the tag return model were accounted for through the use of double-tagged individuals, the distribution of both high- and standard-reward tags, and the completion of an independent controlled experiment to evaluate mortality related to tagging. Annual estimates of F exceeded the short-term management target in both years. Residual patterns suggest that the estimates may actually have been biased low, possibly due to delayed mixing of tagged fish. Thus, despite recently amended fishery regulations, F in the North Carolina southern flounder gill-net fishery still has the potential to greatly exceed targeted levels, which may delay stock recovery. Tag return studies can provide reliable (and nearly real-time) information about F and natural mortality as long as the experimental design addresses specific assumptions related to tagging-induced mortality, tag shedding, and nonreporting of tags.
Postmortem Length Changes in Six Florida Fish Species Stored on Ice
Authors: Chesnes Thomas C. , Waldner Raymond E. , Krahforst Cecilia S. 
Published: October 2009

Abstract
Representatives of six species of fishes belonging to the families Lutjanidae, Centropomidae, Pomatomidae, Scombridae, Carangidae, and Sciaenidae were stored on ice for 6 h after being euthanatized, in order to assess postmortem length changes. Standard length, fork length (where applicable), total length using the relaxed caudal fin method, and rigor mortis were measured immediately after deaths and at 30 min intervals thereafter. Two species, lane snapper Lutjanus synagris and common snook Centropomus undecimalis, showed an increase in mean total lengths during the first hour after death. Common snook continued to increase in mean total length for the duration of the study, while lane snapper subsequently decreased. Declines in mean standard, fork, and total lengths also were observed in bluefish Pomatomus saltatrix, Spanish mackerel Scomberomorus maculatus, and Florida pompano Trachinotus carolinus. Minimal changes in mean standard and total length were observed for spotted seatrout Cynoscion nebulosus. There was little direct correlation between rigor mortis and length variation for any of the studied species. The observed length changes may have implications for both law enforcement personnel and anglers.
Stock Assessment of Scalloped Hammerheads in the Western North Atlantic Ocean and Gulf of Mexico
Authors: Hayes Christopher G. , Jiao Yan , Cortés Enric 
Published: October 2009

Abstract
The status of the western North Atlantic Ocean population of scalloped hammerheads Sphyrna lewini (Sphyrnidae [hammerhead sharks]) was assessed from 1981 through 2005 by using Schaefer (logistic) and Fox surplus-production models. The population declined rapidly before 1996 but began rebuilding in the late 1990s as fishing pressure decreased. The Akaike information criterion for small sample sizes—a test of goodness of fit for statistical models—indicated that the Fox model provided a slightly better fit to the data. Bootstrapped parameter values showed that in 2005 the probability of the scalloped hammerhead's being overfished was greater than 95% (the population was estimated to be 45% of that which would produce the maximum sustainable yield [MSY]) and a 73% probability that overfishing was occurring (fishing mortality was approximately 129% of that associated with the MSY). The size of this population was estimated to be 17% of what it had been in 1981, that is, it has been depleted by about 83% from the virgin stock size. Monte Carlo simulation predicted that the population had a 58% probability of rebuilding in 10 years if the 2005 catch level (4,135 individuals) were maintained and an 85% probability of rebuilding if the 2005 total catch were halved. Sensitivity analyses showed that the stock assessment results were most sensitive to removing the University of North Carolina longline survey index of relative abundance, the method of weighting indices, and excluding fishery-dependent indices of relative abundance.