bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Glycerophosphate-induced mineralization of osteoid does not alter expression of extracellular matrix components in fetal rat calvarial cell cultures
Authors: Lee Kui-Lai , Aubin Jane E. , Heersche Johan N. M. 
Published: February 2010

Abstract
When fetal rat calvarial cells are cultured in medium containing vitamin C, osteoid nodules develop after approximately 15 days of culture. Upon addition of an organic phosphate (β-glycerophosphate, βGP), these nodules mineralize. We have now used this system to explore the suggestion made by others that a negative feedback may exist between matrix mineralization on the one hand and the synthesis of alkaline phosphatase and bone matrix collagen on the other by analyzing the synthesis of these proteins and the levels of their mRNAs in mineralizing and nonmineralizing cultures. Our results indicate that in the osteoid nodule-bone nodule system, matrix mineralization did not affect the mRNA levels for osteopontin, type I collagen, bone sialoprotein, or osteocalcin. Synthesis of total protein and collagen and the osteocalcin content of culture media were also not different in the mineralizing and nonmineralizing cultures. However, alkaline phosphatase mRNA was increased in early mineralizing cultures and alkaline phosphatase activity in the cell layer was also increased in mineralizing cultures. Thus, the hypothesis that a direct negative feedback exists between mineralization and matrix protein synthesis is not supported by our experiments.
Diurnal variation in serum markers of type I collagen synthesis and degradation in healthy premenopausal women
Authors: Hassager Christian , Risteli Juha , Risteli Leila , Jensen Signe Birk , Christiansen Claus 
Published: February 2010

Abstract
There are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 ± 5 years, mean ± SD). Both PICP (p = 0.003) and ICTP (p = 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still unknown.
Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures
Authors: Demulder A. , Suggs S.V. , Zsebo K.M. , Scarcez T. , Roodman G.D. 
Published: February 2010

Abstract
Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [3H]Thymidine incorporation studies showed that SCF increased the proliferation of MNC precursors. These data suggested that SCF was acting on early MNC precursors. We then tested the capacity of SCF to stimulate the formation of colonies of committed precursors for osteoclast-like MNC. SCF (20 pg/ml to 20 ng/ml) enhanced osteoclast precursor formation in unfractionated bone marrow mononuclear cells but was unable to increase osteoclast precursor formation when a highly purified population of hematopoietic precursors was used as the target cells for SCF. These data suggest that SCF works in concert with other factors produced by nonhematopoietic marrow cells to increase the precursor pool for osteoclasts and that other factors, such as 1,25-(OH)2D3, complete the differentiation process to the mature osteoclast.
Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats
Authors: Toolan B.C. , Shea M. , Myers E.R. , Borchers R.E. , Seedor J.G. , Quartuccio H. , Rodan G. , Hayes W.C. 
Published: February 2010

Abstract
Bisphosphonates inhibit osteoclast-mediated bone resorption, but their effects on the mechanical behavior of bone remain uncertain. This study investigated the effects of 4-amino-1-hydroxybutylidene bisphosphonate (AHBuBP) on the biomechanical and morphologic properties of bone in ovariectomized rats. Sprague-Dawley rats (four groups, n = 6) were ovariectomized at 3 months of age. From 7 to 13 months, the groups received vehicle or 0.28, 2.8, or 28 μg/kg of AHBuBP twice weekly through subcutaneous injection. An additional group of control animals (n = 6) received neither surgery nor drug. We determined the stiffness, yield, and ultimate loads of the femoral midshaft, the sixth lumbar (L6) vertebra, and the femoral neck. Geometric properties of the cortical bone were measured from digitized images of the tibial diaphysis at the level of the synostosis. The area fraction of trabecular bone was determined through the midsagittal plane of the fifth lumbar (L5) vertebra. There were no significant differences in the structural properties of the femoral neck and midshaft, with the exception that the medium-dose group had a greater ultimate load than the vehicle group for the femoral midshaft in bending. Cross-sectional analysis of the tibia did not show significant differences in the inertial properties or area. Ovariectomy caused a significant reduction in the stiffness and ultimate load of L6 and in the area fraction of trabecular bone of L5. Using the Tukey method of pairwise comparisons, the mean ultimate load ± standard deviation of the L6 vertebrae from the ovariectomized vehicle group was 30% lower than that from the nonovariectomized control group (276 ± 35 versus 396 ± 63 N, p &lt; 0.05). The mean stiffness was 46% lower (723 ± 206 versus 1327 ± 336 N/mm, p &lt; 0.05), and the area fraction was 41% lower (17.8 ± 5.2 versus 30.0 ± 7.9%, p &lt; 0.05). The high dose of AHBuBP maintained the structural properties of the vertebral bone; the ultimate load (424 ± 55 N), stiffness (1149 ± 145 N/mm), and area fraction (33.7 ± 5.5%) in the high-dose group were all significantly greater than those in the vehicle group but did not differ significantly from those in the control group. We conclude that long-term administration of AHBuBP in rats (started 4 months after ovariectomy) preserves the strength and area fraction of trabecular bone in the lumbar spine in a dose-dependent manner, without evidence of detrimental effects upon the biomechanical or morphologic properties of cortical bone.
Bone and mineral metabolism in the adult guinea pig: Long-term effects of estrogen and androgen deficiency
Authors: Vanderschueren D. , van Herck E. , Suiker A.M.H. , Allewaert K. , Visser W.J. , Geusens P. , Bouillon R. 
Published: February 2010

Abstract
The effects of androgen and estrogen deficiency on skeletal homeostasis were studied in the guinea pig. Male and female adult (7 months old) guinea pigs were either sham operated (9 females and 7 males) or gonadec-tomized [9 ovariectomized (OVX) females and 6 orchidectomized (ORX) males] and sacrificed 4 months later for evaluation of bone mass, bone turnover, and serum calcium homeostasis. Parameters of bone turnover, calcium homeostasis, and vitamin D metabolites were similar in all groups except for increased serum IGF-I concentrations (+30%) in males compared to females. Gonadectomy resulted in a 50% decrease in serum IGF-I concentrations in males only (p &lt; 0.001). Volume, total calcium content, and cortical density of the tibia were significant higher in males than in females. Estrogen deficiency had no effect on bone volume or calcium content. Androgen deficiency resulted in a significant lower volume and calcium content of the tibia and in a lower calcium content of the distal lumbar vertebrae. Single-photon absorptiometry of the tibia showed that only cortical, not trabecular bone density of the tibia was decreased after ORX. Histomorphometric studies of the tibial metaphysis also did not show significant differences in trabecular bone volume between sham-operated and ORX males. We conclude that in adult male guinea pigs androgen deficiency results in a decrease in (cortical) bone volume and content concomitant with decreased IGF-I levels. In female guinea pigs of the same age, estrogen deficiency did not affect total or regional bone mass.
An indirect method of measuring widths suitable for automated bone histomorphometry
Authors: Huffer William E. , Lepoff Ronald B. 
Published: February 2010

Abstract
Orthogonal intercepts from random test lines (OIr), uniformly distributed intercepts (OIu), and areas and lengths (Ar/Le) were measured manually and by computer to determine individual profile and sample widths of artificial profiles and human osteoid seams. Individual widths were equal by Ar/Le and OIu methods. The means of individual profile widths (all methods), of all orthogonal intercepts (OIu and OIr), or of profile widths weighted in proportion to their lengths (Ar/Le) were also equal. Ar/Le and OIu had smaller variance than OIr. Discrepant individual OIu and Ar/Le widths in digitized images were corrected by thresholding and did not significantly affect sample means. Unweighted Ar/Le sample means were 15–44% lower than weighted means. Distributions of osteoid seam widths were not normal, and all but one had more than one mode. We conclude that the Ar/Le method is comparable to direct orthogonal intercept methods and suitable for automated histomorphometry.
A cruciate ligament injury produces considerable, permanent osteoporosis in the affected knee
Authors: Kannus Pekka , Sievänen Harri , Järvinen Markku , Heinonen Ari , Oja Pekka , Vuori Ilkka 
Published: February 2010

Abstract
Bone mineral density (BMD) and clinical status of 42 patients treated surgically 10–11 years earlier for an acute knee ligament injury were determined. The BMD was measured at the spine (L2–4) and the femoral neck, distal femur, patella, proximal tibia, and calcaneus of both lower extremities using dual-energy x-ray absorptiometric (DXA) scanner. The relative BMD results of the injured knee were correlated with sex, age, activity level, knee stability, and functional scores of the patient. In the 11 patients with moderate injury (isolated rupture of the medial collateral ligament), the BMDs of the injured and uninjured extremities were equal. In the 31 patients with severe injury (cruciate ligament rupture), the BMDs were significantly lower in the injured knee: distal femur, −6.0% (p = 0.0000); patella, −9.0% (p = 0.0000); and proximal tibia, −3.3% (p = 0.0012). Neither the femoral neck nor the calcaneus showed any differences. There were no significant differences either between men and women or between patients with different activity levels. The relative BMDs of the injured knee did not correlate with age or static knee stability but correlated significantly (r = 0.42–0.78, p &lt; 0.01–0.001) with the functional scores of the same knee: the better the knee function in comparison with the healthy knee, the higher the relative BMD. The spinal BMDs corresponded with the age-adjusted reference values of the used densitometry. In conclusion, a severe knee ligament injury results in permanently decreased BMD in the injured knee. Other parts of the same extremity and lumbar spine are not affected. The observed decrease (3–9%) is clinically important with respect to age-related bone loss of 1%/year after the age of 35 years. Additional follow-up is needed to determine any increased risk of osteoporotic knee fracture.
Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13–14
Authors: Labuda Malgorzata , Fujiwara T. Mary , Ross Michelle V. , Morgan Kenneth , Garcia-Heras Jaime , Ledbetter David H. , Hughes Mark R. , Dr. Glorieux Francis H. 
Published: February 2010

Abstract
We have localized the locus for the vitamin D receptor (VDR) responsible for hypocalcemic vitamin D-resistant rickets (HVDRR), close to the pseudovitamin D-deficient rickets (PDDR) locus, another disorder related to impaired vitamin D metabolism. PDDR (formerly vitamin D dependency type I, VDD1) was recently mapped to human chromosome 12q14 by linkage analysis. Here we report on the assignment of VDR to 12q13–14 by in situ hybridization and by linkage analysis. Linkage analysis between VDR, PDDR, and several RFLP markers show close linkage, with no recombination (θ = 0) between VDR and PDDR (Z = 1.94), a COL2A1 haplotype (Z = 4.03), ELA1 (Z = 0.98), and D12S15 (Z = 4.17). The analysis of extended haplotypes in one of the PDDR families provides evidence for recombination between VDR and PDDR and localizes VDR together with COL2A1 proximal to PDDR. Complete allelic association detected between VDR and COL2A1 loci on PDDR chromosomes and lower association between VDR and PDDR suggests a VDR location very close to COL2A1 and one more distant to PDDR. We propose the following order of loci: (VDR, COL2A1), (PDDR, ELA1, D12S15), D12S4, (D12S14, D12S17), D12S6. Thus, two clearly distinct loci involved in the control of vitamin D activity map close to each other in the region 12q13–14.
Bone resorption and formation on the periosteal envelope of the ilium: A histomorphometric study in healthy women
Authors: Balena Raffaella , Shih Mei-Shu , DR. Parfitt A. Michael 
Published: February 2010

Abstract
Continuation of net periosteal bone gain after cessation of longitudinal growth has been inferred from sequential radiographic morphometry. Accordingly, we performed histomorphometry of the periosteal surfaces of transilial bone biopsies from 57 healthy women aged 24–74 years, 29 premenopausal and 28 postmenopausal. Compared to the endocortical surface, the extents of eroded and osteoid surfaces were very similar, but the extents of osteoclast- and osteoblast-covered surfaces were 80–90% smaller, and both wall thickness and osteoid thickness were about 30% lower. Double tetracycline labels were present in only 11 cases. The second (demethylchlortetracycline) label was almost four times as long as the first (oxytetracycline) label, a much greater difference than on the endocortical surface, so that the extent of mineralizing surface was based only on the second label. Even so, adjusted apposition rates and bone formation rates were only about 20% of the endocortical values, and unlike the endocortical surface, formation rates were not higher in the postmenopausal than in the premenopausal women. Resorption, reversal, and formation periods were each much longer than on the endocortical surface. There was no correlation between periosteal and endocortical values for any variable. At least 54% of total cement line length was scalloped, implying reversal of remodeling direction from resorption to formation, and at least 18% of total cement line length was smooth, implying temporary arrest of bone formation. Convincing evidence of modeling, related to growth or mechanical stimulation, was not observed. We conclude (1) periosteal bone turnover occurs by remodeling rather than modeling; it is much slower than endosteal turnover and extends less far from the surface, (2) periosteal bone formation is probably discontinuous with long periods of interruption, and (3) periosteal bone cell recruitment and activity appear to be relatively uninfluenced by the hormonal changes of aging and menopause; presumably local factors, possibly biomechanical, are more important.
Journal of Bone and Mineral Research
Authors: Ypey Dirk L. , Weidema Adam F. , Höld Karin M. , Van Der Laarse Arnoud , Ravesloot Jan H. , Van Der Plas Arie , Nijweide Peter J. 
Published: February 2010

Abstract
Embryonic chick bone cells express various types of ionic channels in their plasma membranes for as yet unresolved functions. Chick osteoclasts (OCL) have the richest spectrum of channel types. Specific for OCL is a K+ channel, which activates (opens) when the inside negative membrane potential (Vm) becomes more negative (hyperpolarization). This is consistent with findings of others on rat OCL. The membrane conductance constituted by these channels is called the inward rectifying K+ conductance (GKi), or inward rectifier, because the hyperpolarization-activated channels cause cell-inward K+ current to pass more easily through the membrane than outward K+ current. Besides GKi, channels, OCL may express two other types of voltage-activated K+ channels. One constitutes the transient outward rectifying K+ conductance (GKto), which is activated upon making the membrane potential less negative (depolarization) but has a transient nature. This conductance favors transient K+ conduction in the cell-outward direction. The GKto also occurs in a small percentage of cells in osteoblast (OBL) and periosteal fibroblast (PFB) cultures. The other OCL K+ conductance, the GKCa, is activated by both membrane depolarization and a rise in [Ca2+]i. GKCa channels are also present in the other chick bone cell types, that is, OBL, osteocytes (OCY), and PFB. Furthermore, in excised patches of all bone cell types, channels have been found that conduct anions, including CI− and phosphate ions. These channels are only active around Vm = 0 mV. While searching for a membrane mechanism for adaptation of bone to mechanical loading, we found stretch-activated channels in chick osteoclasts; other investigators have found stretch-activated cation channels (K+ or aselective) in rat and human osteogenic cell lines. In contrast to other studies on cell lines or OBL from other species, we have not found any of the classic macroscopic voltage-activated calcium conductances (GCa) in any of the chick bone cells under our experimental conditions. However, our fluorescence measurements of [Ca2+]i in single cells indicate the presence of Ca2+ conductive pathways through the plasma membrane of osteoblastic cells and osteoclasts, consistent with other studies. We discuss possible roles for GKi, GKCa, and anion channels in acid secretion by OCL and for stretch-activated channels in OCL locomotion.
Journal of Bone and Mineral Research
Authors: Carter Dennis R. , Orr Tracy E. 
Published: February 2010

Abstract
The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The results of many previous computer models for endochondral ossification and bone modeling and remodeling are reviewed. These studies support the view that simple stress-related mathematical algorithms or “construction rules” can be used to emulate normal skeletal development and architectural construction. Such mathematical rules presumably represent the net result of biophysical phenomena influencing cell metabolism and biosynthetic activity. These rules are also successful in describing the adaptation of adult bone to changes in tissue stresses. The findings suggest that stress-related functional adaptation in mature bones may be merely the adult manifestation of the same mechanical construction rules that guide and constrain normal development.
Journal of Bone and Mineral Research
Authors: Cordey Jacques , Schneider Marina , Belendez Christina , Ziegler Walter J. , Rahn Berton A. , Perren Stephan M. 
Published: February 2010

Abstract
Proximal femur fractures in the elderly lead to a high rate of hospitalization. In studying the operative treatment of such fractures, it is first necessary to understand the relationship between the morphologic properties of this part of the femur (related to both geometry and density) and its mechanical properties. Numerous investigations showed that femoral strength correlates with bone mass; however, the dimension of the bones was not taken into account. We measured the relationship between the stiffness of the proximal femur under physiologic load and its geometry and density. Conventional x-rays and quantitative computed tomography (QCT) were carried out on pairs of human cadaver femora. Eight pairs were instrumented with strain gauges. Bones were subjected to an eccentric load that simulates moderate weight bearing (single-leg stance), and the strain parallel to the bone axis was plotted as a function of the load applied. An apparent bone stiffness was calculated as the ratio between the strain gradient within the section and the load applied. Strong correlation was found between x-ray densitometry and QCT. The bone stiffness also correlates strongly with the geometry (area) and slightly with bone mass; however, an unexpectedly low correlation was found between stiffness and density. We chose stiffness as a mechanical parameter (not strength) because it describes the “normal” bone behavior under load. Our results clearly demonstrate that the cross-sectional size of the bones must be taken into account when establishing the relationship between the mechanical characteristics of the bone and its morphology. In accordance with previous predictions, our results support that bone loss due to osteoporosis is compensated for by an increase in bone diameter.
Cultured circulating mononuclear cells from osteopetrotic infants express the osteoclast-associated vitronectin receptor and form multinucleated cells in response to 1,25-dihydroxyvitamin D3
Authors: Cournot Giulia , Petrovic Milka , Trubert Claire-Lise , Cormier Catherine , Girault Danielle , Fischer Alain , Garabedian MichÈLe 
Published: February 2010

Abstract
Malignant osteopetrosis is characterized by impaired osteoclast activity. Osteoclasts derive from hematopoietic stem cells. In osteopetrosis, marrow cavities fail to develop, resulting in extramedullary hematopoiesis and the presence of stem cells in the bloodstream. Resistance to 1,25-(OH)2D3 may be involved in the pathogenesis of the disease. Sensitivity to 1,25-(OH)2D3, calcitonin sensitivity, and expression of the osteoclast-associated vitronectin receptor (VR) was examined in cultures of circulating mononuclear cells of seven osteopetrotic infants (1.5–6 months old). Since peripheral blood from age-matched children contains few stem cells, umbilical cord blood was used as control. Mononucleated cells were isolated by the Ficoll-Hypaque method and cultured (106 cells per ml) in α-MEM containing 20% horse serum in presence or absence of added 1,25-(OH)2D3. VR was identified by immunochemical staining with MAb 23C6. 1,25-(OH)2D3 at 10−8 M significantly stimulated the formation of multinucleated cells (MNC) in cultures from all osteopetrotic patients and cord blood samples. Cells from three of five patients responded to 10−9 M 1,25-(OH)2D3, the minimal stimulatory concentration for cord blood. Salmon calcitonin (100 ng/ml) partially inhibited the 10−8 M 1,25-(OH)2D3-induced MNC formation in cultures from three of six patients and in cultures of all cord blood samples. In both types of cultures mononuclear cells and MNC cross-reacted with MAb 23C6, and 1,25-(OH)2D3 concentration did not influence the number and percentage of these cells. This study does not support the hypothesis of 1,25-(OH)2D3 resistance in osteopetrotic infants and shows that mononuclear cells expressing VR, possibly osteoclast progenitors, develop in cultures of circulating mononuclear cells from these infants. 1,25-(OH)2D3 may not be closely involved in VR expression.