bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulatory effect of TGF-β on anionic glycoconjugate synthesis by rat calvarial cells: Specificity, uncoupling of cell density dependence, and modulation by chondroitin sulfate
Authors: Professor Anastassiades Tassos P. , Chan Catherine 
Published: February 2010

Abstract
Anchorage-dependent cultures of a population of cells derived from the outer part of the rat calvaria demonstrated decreased net accumulation of radiolabeled chondroitin sulfate (CS) and hyaluronic acid (HA) per cell as the cell density of the cultures increased. The addition of TGF-β1 resulted in large stimulations of the net CS, but not of the net HA, accumulating in the medium at all cell densities and an abolition of the density-dependent effect. These effects were largely due to increases in newly synthesized CS appearing in the medium. Supplementation of the culture media with CS had complex but relatively small effects on the stimulation of the net accumulation of radiolabeled medium CS by TGF-β1. The addition of TGF-β1 also resulted in a biphasic effect on cell growth that depended on the plating density, but cell growth differences could not account for the marked stimulation of CS synthesis by TGF-β1. Experiments with cycloheximide and β-xyloside and isolation of the intact anionic glycoconjugates (AG) indicated that although synthesis of core protein was the limiting factor in CS synthesis, TGF-β1 stimulated the synthesis of CS chain when sufficient β-xyloside acceptor was available. The overall results suggest that, in this cell system, the action of TGF-β1 on the synthesis of the major extracellular AGs is characterized by a relatively specific upregulation of CS proteoglycan (PG) synthesis and an uncoupling of the inhibitory effect of high cell density on CS PG synthesis.
Effects of interleukin-4 on the formation of macrophages and osteoclast-like cells
Authors: Riancho José A. , Zarrabeitia María T. , Mundy Gregory R. , Yoneda Toshiyuki , González-Macías Jesus 
Published: February 2010

Abstract
The lymphokine interleukin-4 (IL-4) is an important lymphocyte growth factor, and it also has a modulatory role on hematopoiesis. It was recently reported that IL-4 has an inhibitory effect on bone resorption in vitro, but the underlying mechanisms are not well known. We studied its effects on the formation of osteoclast-like cells in mouse bone marrow cultures and in cocultures of spleen cells and stromal cells. The addition of recombinant mouse IL-4 (0.01–10 ng/ml) induced a marked dose-dependent inhibition on the formation of TRAP-positive multinucleated cells (MNC) in bone marrow cultures. The effect was blocked by anti-IL-4 antibodies and was not related to a decreased production of IL-6. The inhibitory effect required the presence of IL-4 during the second half of the culture period. Time course experiments showed that IL-4 impaired the formation of osteoclast-like cells rather than inducing the disappearance of previously formed cells. This inhibitory effect was associated with increased numbers of esterase-positive cells. Moderately high doses of IL-4 (1–10 ng/ml) also induced the formation of abundant macrophage polykaryons that did not form resorption pits. IL-4 had a similar inhibitory effect on the formation of osteoclast-like cells in cocultures of mouse spleen cells and stromal cells. Our results suggest that IL-4 acts on uncommitted macrophage-osteoclast precursors, inducing a preferential differentiation toward the macrophage lineage and thus decreasing the formation of osteoclast-like cells.
Characterization of radioiodinated recombinant human TGF-β1 binding to bone matrix within rabbit skull defects
Authors: Richardson Louise , Zioncheck Thomas F. , Amentoè Edward P. , Deguzmanè Leo , Leeè Wyne P. , Xuè Yvette , Beckè L. Steven 
Published: February 2010

Abstract
Bone healing is regulated in part by the local production of TGF-β1 and other growth factors produced by cells at the site of injury. The single application of recombinant human TGF-β1 (rhTGF-β1) to calvarial defects in rabbits induces an accelerated recruitment and proliferation of osteoblasts within 3 days. This ultimately results in the formation of new bone and the complete closure of the defect within 28 days. The persistence and localization of [125I]rhTGF-β1 within an osseous defect was investigated after applying a single dose of [125I]rhTGF-β1 formulated in a 3% methylcellulose vehicle. Normal bone encompassing the defect site, the periosteum, and the gel film covering the dura were harvested at 0, 4, 8, and 24 h and 3, 7, and 16 days after [125I]rhTGF-β1 application. The defect site-associated radioactivity was quantitated, visualized by autoradiography, and characterized by TCA precipitation and SDS-PAGE. Radioactivity was observed in autoradiographs of gross specimens, histologic sections of the bone matrix, and periosteal tissue surrounding the defect. There was a time-dependent decrease in TCA-precipitable radioactivity; however, radioactivity was still associated with the bone matrix 16 days after application of [125I]rhTGF-β1. SDS-PAGE and autoradiography of the radioactivity in homogenized bone and periosteal samples revealed a 25 kD band, suggesting that the radioactivity remaining at the defect site represented intact [125I]rhTGF-β1. Results of this study indicate that rhTGF-β1 may bind tightly to bone matrix in its active form, and this binding may be associated with the observed increase in osteoblast number and bone matrix within the calvarial defects.
Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue
Authors: Lakatos Peter , Caplice Matthew D. , Khanna Vikram , Stern Paula H. 
Published: February 2010

Abstract
The mechanism of action of thyroid hormones on bone is still not clear. At low concentrations, they stimulate bone formation; at high concentrations, they elicit bone resorption in vitro and in vivo. In the present study we investigated the effect of T3 and T4 as well as their active and inactive analogs (TRIAC, SKF L-94901, rT3, and DIT) on the IGF-I and TNF-α content in the medium of UMR-106 rat osteoblastic cells and fetal rat limb bones. In the dose-response studies, a biphasic increase in medium IGF-I was observed in both cells and limb bones, with peak stimulatory concentrations of 10−8 M for T3 and 10−7 M for T4 in both systems. At higher concentrations, at which thyroid hormones elicit bone resorption, the stimulatory effect diminished and finally was no longer detectable. The active analogs TRIAC and SKF L-94901 also enhanced IGF-I release in UMR-106 cells. The inactive compounds rT3 and DIT failed to increase IGF-I in these cultures. The protein content of the cell culture wells exposed to high concentrations of thyroid hormones was similar to those containing low concentrations, indicating that the decrease in IGF-I content at high doses was not due to toxic effects. This was also confirmed by trypan blue exclusion. Time course studies with UMR-106 cells revealed a significant increase in medium IGF-I after 2 days of incubation. No significant further increase was observed after this up to 5 days of culture. In contrast, the medium of limb bone cultures showed a linear increase in IGF-I content up to 7 days of culture. No TNF-α production was observed in either UMR-106 cells or fetal limb bones. Also, no increase in medium TNF-α levels was seen in response to thyroid hormones. Based on our results, we conclude that IGF-I may be responsible for some of the anabolic effects of thyroid hormones in bone tissue, but TNF-α, at least in the models we used, does not play a role in the mediation of thyroid hormone action.
Effects of the bisphosphonate tiludronate on bone resorption, calcium balance, and bone mineral density
Authors: Dr. Ammann Patrick , Rizzoli René , Caverzasio Joseph , Shigematsu Takashi , Slosman Daniel , Bonjour Jean-Philippe 
Published: February 2010

Abstract
Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decrease in retinoid-stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time- and dose-dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.
Evidence that a non-RGD domain in rat osteopontin is involved in cell attachment
Authors: van Dijk Simon , D'Errico John A. , Somerman Martha J. , Farach-Carson Mary C. , Butler William T. 
Published: February 2010

Abstract
The bone sialoprotein osteopontin (OPN) promotes cell attachment and spreading through its RGD (Arg-Gly-Asp) sequence. To study additional regions of OPN involved in cell attachment, peptides of rat OPN were evaluated for their capacity to mediate cell binding to wells in vitro. Human gingival fibroblasts were incubated on microtiter plates coated with either OPN or OPN peptides. A peptide of Mr 28 kD, obtained after digestion with endoproteinase Arg-C and isolated by reversed-phase HPLC, enhanced cell attachment to a similar degree as OPN. Sequence analysis showed that the amino terminus of the 28 kD peptide starts at Ser142 and therefore does not contain the RGD cell attachment sequence (residues 128–130). Cell attachment mediated through both OPN and the 28 kD peptide was blocked by the addition of GRGDSPA peptides or LM-609, a monoclonal antibody to the integrin αVβ3, a receptor for vitronectin. A variant peptide, GRG-ESPA, did not alter cell attachment. Based on these observations, we conclude that (1) binding of OPN and the 28 kD peptide to fibroblasts involves binding to αVβ3, (2) a site other than the RGD sequence on OPN is also involved in binding to integrins, and (3) the binding of this second site to αVβ3 is inhibited by RGD-containing peptides.
Journal of Bone and Mineral Research
Authors: Robey Pamela Gehron , Fedarko Neal S. , Hefferan Theresa E. , Bianco Paolo , Vetter Ulrich K. , Grzesik Wojciech , Friedenstein Alexander , van der Pluijm Gabri , Mintz Keith P. , Young Marian F. , Kerr Janet M. , Ibaraki Kyomi , Heegaard Anne-Marie 
Published: February 2010

Abstract
The organic matrix of bone contains several protein families, including collagens, proteoglycans, and glycoproteins, all of which may be extensively modified by posttranslational events, such as phosphorylation and sulfation. Many of the glycoproteins contain Arg-Gly-Asp (RGD), the integrin-binding sequence, within their structure, whereas other constituent proteins contain gamma-carboxyglutamic acid. The deposition of bone matrix by cells in the osteoblastic lineage is regulated by extrinsic factors, such as systemic and local growth factors and physical forces, and factors that are intrinsic to the cell, such as position in the cell cycle, maturational stage, and developmental age of the donor. Recent studies of several bone matrix gene promoters have identified cis- and trans-acting elements that are responsible for gene activity, although the precise sequence of regulatory events is not known. Development of in vitro assays, coupled with studies of the appearance of these proteins during development in vivo, provides insight into the functions of these proteins during the various stages of bone metabolism. Potential roles for these proteins include proliferation and maturation of stem cells, formation of matrix scaffolding elaborated by bone-forming cells, modeling, and remodeling. Changes in the functional properties of the extracellular matrix may be involved in a variety of disease processes, including osteoporosis and oral bone loss.
Journal of Bone and Mineral Research
Authors: Mundy Gregory R. 
Published: February 2010

Abstract
Osteoporosis and periodontal disease both represent examples of abnormal bone remodeling. As knowledge of the cellular and molecular events in the normal bone remodeling process has accumulated in the last decade, better understanding of the pathophysiology of bone loss associated with periodontal disease and with aging has occurred. This short review does not attempt to include all aspects of this topic but covers specific areas in which there have been recent advances. (1) Observations made in the last few years have indicated that a hierarchy of both receptor and nonreceptor tyrosine kinases may be involved in normal osteoclastic bone resorption and that certain members of these tyrosine kinase families may mediate cytokine effects. Studies in the op/op variant of murine osteopetrosis have shown that normal production of monocyte-macrophage colony-stimulating factor 1 (M-CSF, also called CSF-1) and activation of its receptor (the receptor tyrosine kinase c-fms) are required for normal osteoclast formation. (2) Studies in mice made deficient in nonreceptor tyrosine kinase by gene knockout have shown that expression of this nonreceptor tyrosine kinase is required for normal osteoclast action and ruffled border formation, although not for osteoclast formation. (3) Recent studies have shown that in addition to protaglandins of the E series, other arachidonic acid metabolites may be involved in normal and abnormal osteoclastic bone resorption. 5-Lipoxygenase metabolites, the leukotrienes, stimulate isolated osteoclasts to form resorption pits as well as cause osteoclastic bone resorption in organ cultures of neonatal mouse calvariae. These compounds, which are unstable in tissue culture media, are readily inhibitable by agents that inhibit 5-lipoxygenase enzymes. Since they accumulate in chronic inflammatory cells, they may be important in bone remodeling associated with periodontal disease. (4) Recently, a new growth regulatory factor for osteoclasts has been described. This factor, called the osteoclastpoietic factor (OPF), is likely akin to the colony-stimulating factors for the formed elements of the blood, since the osteoclast shares a common precursor with these cells. OPF enhances the differentiation of osteoclasts from committed precursors. Its role in normal and abnormal bone remodeling is still to be determined. (5) Recent studies using prolonged cultures of fetal rat calvarial cells have shown that members of the TGF-β superfamily (TGF-β and the BMPs) may work in concert to stimulate normal bone formation. In this in vitro model culture system, TGF-β enhances cell proliferation but inhibits differentiated function. In contrast, BMP-2, a prototype for the BMP family, enhances differentiated function in these cells, including expression of osteocalcin, alkaline phosphatase, and the formation of bone nodules. For more comprehensive reviews of the role of cytokines in bone remodeling, the reader is referred to Mundy (1993), Manolagas and Jilka (1992), and Canalis et al. (1989).
Journal of Bone and Mineral Research
Authors: Kimmel Donald B. 
Published: February 2010

Abstract
This article integrates engineering principles with skeletal biology to describe skeletal strength homeostasis. Skeletal strength revolves around its perceived mechanical usage. Mass, geometric properties, and fatigue damage burden are the principal determinants of structural strength. Bone cells form sensor and effector systems that monitor usage and adjust strength and stiffness by changing mass, geometric properties, and fatigue damage burden. The bone lining cell–osteocyte complex is the sensor; the bone modeling and remodeling systems are the effectors. Deformation and fatigue damage in bone are the signals received by the sensor. Accumulated energy in the sensor's cytoskeleton determines the rate at which the sensor sends messages to the effectors. The activity of both effector systems is proportional to the rate of incoming messages. Modeling raises bone strength and stiffness by improving geometric properties as it adds bone where customary deformation is greatest. Remodeling improves bone strength by replacing fatigue-damaged areas without mass changes. Bone removed during modeling and remodeling comes from sites where the impact on bone strength and stiffness is least. Hormones and agents alter the rigidity of the cytoskeleton and, thus, its capacity to deform and store energy. Osteopenic agents make it more rigid, causing detection of fewer deformations and transmission of fewer loading signals to the effector. Osteotropic agents decrease the rigidity of the cytoskeleton, causing detection of more strain events and transmission of more loading signals to the effector. Agent treatment thus establishes false conditions of disuse or hyperuse.
Journal of Bone and Mineral Research
Authors: Aufdemorte Thomas B. , Boyan Barbara D. , Fox W. Casey , Miller Dennis 
Published: February 2010

Abstract
Recent data have suggested that there may be a relationship between osteoporosis and oral bone loss. Both diseases are major public health problems of enormous magnitude, but their relationship is poorly understood. This is due to their complex pathogenesis and the fact that coexisting periodontal disease, loss of the dentition, site-specific variability in anatomy and bone density, as well as aging and many other factors complicate the development and progression of bone loss relative to each. The focus of this article is to review the characteristics of animals that are suited for studies of the relationship of osteoporosis and oral bone loss to better understand their relationship.
Journal of Bone and Mineral Research
Authors: Webber Richard L. 
Published: February 2010

Abstract
Practical use of images for diagnosis of osseous, abnormalities presumes cost-effective technology that targets known physiologic processes. The most obvious modalities for such applications are radiographic, and the newest are characterized by quantitative methods expressed both tomographically and by means of digital subtraction registered in two and three dimensions. Quantitative nuclear medicine and possibly electron spin resonance spectroscopy also appear promising. New analytic techniques for interpreting osseous images include characterization of trabecular patterns by fractal descriptors and micromorphometry.
Journal of Bone and Mineral Research
Authors: Baylink David J. , Finkelman Richard D. , Mohan Subburaman 
Published: February 2010

Abstract
During the past decade we and others have shown that bone is a storehouse for growth factors. Accordingly, bone contains a number of growth factors including insulin-like growth factors I and II (IGF-I, IGF-II) transforming growth factor (TGF-β1, TGF-β2), platelet-derived growth factor, basic and acidic fibroblast growth factor, and bone morphogenetic proteins (BMPs). Osteoblasts have been shown to produce many of these growth factors, which then act in an autocrine and paracrine fashion. The production of these growth factors is regulated by both systemic hormones and local mechanical stress. Recent studies on the relative distribution of bone growth factors during different physiologic and pathologic situations indicate that the concentration of bone growth factors is not invariant and provide indirect evidence that growth factors deposited in bone have physiologic significance. In addition, many of these bone growth factors have been shown to increase bone formation either systemically or locally in vivo. Based on the past findings, we propose that different growth factors may have a specific role in regulating proliferation and differentiation of different stages of osteoblast lineage cells and play important roles in the local regulation of bone formation.
Journal of Bone and Mineral Research
Authors: Ott Susan M. 
Published: February 2010

Abstract
The bisphosphonates are analogs of naturally occurring pyrophosphate. They appear to block bone resorption much more than mineralization. A series of compounds has been investigated. These have antiresorptive potencies ranging from 1 to 10,000. So far, structure-function relationships have eluded definition. These drugs increase the bone density in women with postmenopausal osteoporosis by about 5%-10% over 1 year. The bone density then appears to plateau, but most studies are of short duration. Improved bone density does not necessarily result in stronger bone, but no studies have had adequate power to assess fracture incidence. Bone formation rates decrease as measured histomorphometrically. This occurs while the bone density is improving, which implies an inhibition of bone resorption that is probably due to direct toxicity to the osteoclasts. Etidronate blocks mineralization as well as resorption and can cause osteomalacia, which is not seen with low-dose cyclical etidronate or with the second-generation compounds. The long-term effects of interfering with the remodeling cycle are still not known. Subtle side effects may be those on the bone itself. These might go undetected, since bone pain or fractures usually are atributable to the underlying disease.
Changes in bone mass early after kidney transplantation
Authors: Horber F.F. , Casez J.P. , Steiger U. , Czerniak A. , Montandon A. , Jaeger PH 
Published: February 2010

Abstract
Renal transplant patients exhibit increased rates of trabecular bone fractures, probably due to glucocorticoid-induced osteopenia, which is known to occur within 6 months after kidney grafting. This mineral loss at a mostly trabecular site (lumbar spine) contrasts with a gain at the radius, which consists mainly of cortical bone. However, the early effects of kidney transplantation on the other parts of the human skeleton and the time course of these changes during the first 5 months after transplantation remain unknown. Therefore, 34 kidney transplant recipients were prospectively followed immediately after kidney grafting (12 ± 1 days, mean ± SEM, and then on a monthly basis up to 152 ± 3 days) and compared with 34 normal healthy volunteers matched for age, sex, and body mass index. Bone mineral measurements of whole body (n = 34), lumbar spine (n = 32), and upper femur (n = 23) were performed using dual-energy x-ray absorptiometry (Hologic QDR 1000W). At time of transplantation, lumbar bone mineral density (BMD) and BMD of the upper femur were lower (p &lt; 0.01) in female but not male patients compared with controls. Lumbar BMD decreased by 1.6 ± 0.2% per month in both sexes (p &lt; 0.01), whereas BMD of upper femur further decreased in males (p &lt; 0.01) but only tended to decrease in females. At time of transplantation, whole-body bone area (BA), bone mineral content (BMC), and BMD were decreased by about 8, 15, and 9%, respectively, in patients compared with controls (p &lt; 0.01). Compartmental analysis revealed similar reductions in BMD and BMC at trunk, head, and limbs, whereas BA was reduced only at limbs (p &lt; 0.01). During the 152 ± 3 days of observation, BMC and BMD of limbs remained essentially unchanged, whereas BA of limbs increased (p &lt; 0.01) and BA, BMC, and BMD of trunk and head decreased (p &lt; 0.01). In conclusion, within 5 months after successful kidney transplantation resulting in good renal function, about 41 g bone mineral is lost, mostly due to losses in the trabecular bone compartment (i.e., about 10%). Longitudinal trials to prevent trabecular bone loss during the phase of terminal renal failure and during the first half-year following transplantation are urgently needed to develop rational and effective therapeutic strategies in patients on dialysis and kidney transplant patients.