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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 73 records · Page 4Linked to original sources

Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency.

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.

Aged↗

The mechanism of the stabilization of the hexagonal II (HII) phase in phosphatidylethanolamine membranes in the presence of low concentrations of dimethyl sulfoxide.

Dimethyl sulfoxide (DMSO), a water-miscible organic solvent, has been used as a cryoprotectant for cells. It is known that DMSO stabilizes the HII phase of phosphatidylethanolamine (PE) membranes rather than the Lalpha phase, while most other water-miscible organic solvents such as acetone and ethanol destabilize the HII phase. To elucidate the mechanism for this stabilizing effect of DMSO on the HII phase, we have investigated its effects on the structures and physical properties of PE membranes. X-ray diffraction data indicated that dipalmitoleoylphosphatidylethanolamine (DPOPE) membranes in H2O at 20 degrees C were in the Lalpha phase and that an Lalpha to HII phase transition occurred at X=0.060 (mole fraction of DMSO) in water/DMSO mixtures. As the DMSO concentration increased, the basis vector length of the dioleoylphosphatidylethanolamine (DOPE)/ 16 wt% tetradecane membrane and also of the DPOPE/ 16 wt% tetradecane membrane in the HII phase decreased, suggesting that the spontaneous curvature of these membranes increased. We have also investigated the effects of DMSO on the physical properties of the PE membranes, and compared them with those of acetone. As the DMSO concentration increased, the excimer to monomer fluorescence intensities of pyrene-phosphatidylcholine in the PE membranes decreased, indicating that the membrane fluidity decreased, and also the generalized polarization value of the Laurdan fluorescent probe in the DPOPE membrane increased, indicating that the polarity of the membrane interface decreased. On the other hand, acetone had the opposite effects to DMSO. The interaction free energy between the membrane surface segments and solvent increased with an increase in DMSO concentration. It decreased the amount of solvent in the membrane interface, inducing an increase in the spontaneous curvature. This can reasonably explain the effects of DMSO on the phase stability and the physical properties of the membranes.

2-Naphthylamine↗

Evolution from pretangle neurons to neurofibrillary tangles monitored by thiazin red combined with Gallyas method and double immunofluorescence.

Double immunofluorescence for paired helical filament (PHF)-tau (AT8) and ubiquitin, enhanced by catalyzed reporter deposition amplification, was combined with thiazin red (TR), a fluorochrome, which has an affinity to fibrillary structures such as neurofibrillary tangles (NFTs). After recording these triple-fluorescent images, sections were subjected to the Gallyas silver impregnation method, so that four different staining properties could be compared on the same structure. Among pyramidal neurons quantified in the hippocampus from six cases of Alzheimer's disease, 60.3% were positive for ubiquitin, and were consistently positive for TR. TR-positive neurons (77.1%) harbored fibrillary structures in the cytoplasm and were always positive for the Gallyas stain, which stained the largest number of legions (94.5%). AT8-positive neurons without fibrillary structure were negative for TR (11.6%, pretangle neurons). Some of the pretangle neurons were positive for the Gallyas stain even without fibrillary structures. Appearance of TR stain and ubiquitin in NFTs, but not in pretangle neurons, suggests that ubiquitin is integrated into tau-positive neurons after their transformation into NFTs. Because TR-positive NFTs sometimes lacked ubiquitin-like immunoreactivity, involvement of ubiquitin may not be an early event during NFT formation. This combined method is now found useful in determining how molecules other than tau are involved during the evolution from tau-positive neurons to NFTs in various neurological disorders characterized by the deposition of tau.

Aged↗

Acute up-regulation of brain-derived neurotrophic factor expression resulting from experimentally induced injury in the rat spinal cord.

Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of trophic factors, has multiple functions including a role in the promotion of neuronal survival and nerve fiber elongation in both the central and the peripheral nervous systems. We assessed the expression of endogenous BDNF following an experimentally induced compression injury to the spinal cord. Expression of BDNF mRNA was increased following the spinal cord injury; reaching maximum levels 24 h after the injury. Expression of BDNF mRNA returned to the levels observed in sham-operated control animals within 3 days of the injury. Using the in situ hybridization technique, we observed a wide distribution of BDNF expression among the different cell types in the spinal cord, including motor and sensory neurons, and in glia cells, including astrocytes. We also observed expression of BDNF in putative macrophages and/or microglia; however, this effect was not observed until day 7 following spinal cord injury. These results suggest that BDNF is synthesized in both neurons and astrocytes during the acute response to injury to the spinal cord, functioning in a mainly neuroprotective role. This is followed by a later phase of expression in which BDNF is produced by macrophages and/or microglia, apparently functioning in a restorative capacity.

Animals↗

Different conformation of neuronal tau deposits distinguished by double immunofluorescence with AT8 and thiazin red combined with Gallyas method.

Different kinds of tau deposits were quantitatively investigated with thiazin red (TR), a fluorochrome that binds to fibrillary structures like neurofibrillary tangles (NFTs), in brains obtained at autopsy from patients with Alzheimer's disease (AD), Pick body (PB) disease, corticobasal degeneration (CBD) or diffuse NFTs with calcification (DNTC). After recording double-labeling fluorescence images with anti-paired helical filament tau (AT8) and TR, the sections were subjected to Gallyas method (GAL). This enabled three different staining properties to be compared on the identical neuron. AT8-positive neocortical neurons of AD and DNTC were fibrillary and uniformly positive for TR and GAL, consistently forming NFTs. NFTs lacking AT8 immunoreactivity (IR) were more frequent in DNTC than in AD, suggesting that evolution of NFTs is more accelerated in DNTC. Scarce TR staining in tau-positive neocortical neurons of CBD suggests their paucity of fibrillary structure. Since the affinity of TR for PB was not consistent, this may be dependent not only on the amount but also the characteristics of fibrillary structures. PBs were further characterized by the scarcity of GAL staining. This approach, which quantitatively clarifies differences between AT8-IR, TR and GAL, provides a morphological basis for further investigations of the different conformational states of tau from its deposition to fibril formation of various types.

Aged↗

Progressive supranuclear palsy on Guam.

This is the first report demonstrating that progressive supranuclear palsy (PSP) exists on Guam. This 75-year-old Guamanian Chamorro patient with slight dementia and rigidity with restriction of ocular up gaze was diagnosed as parkinsonism-dementia complex (PDC) of Guam clinically. However, neurofibrillary tangles (NFTs) were scarcely seen in the cerebral cortices and hippocampus, but many NFTs, composed of 15-17 nm straight tubules, were detected in the subthalamic nucleus and brain stem. A large number of tuft-shaped astrocytes were observed in the putamen and motor cortex, and numerous argyrophilic grains were seen in the CA1 and subiculum. These pathological findings are different from those of PDC and consistent with PSP. The present case indicates that PSP and PDC clinically resemble each other, and that precise neuropathological examination is indispensable for the final diagnosis of the patient with parkinsonism, dementia and disturbance of vertical external ocular movement.

Aged↗

The rice retrotransposon Tos17 prefers low-copy-number sequences as integration targets.

The rice retrotransposon Tos17 is highly activated by tissue culture. To evaluate the impact of transposition of Tos17 on the rice genome and examine its utility for insertional mutagenesis, more than 100 sequences flanking newly transposed Tos17 copies were characterised. The 5-bp target-site duplications flanking Tos17 did not show any consensus sequence, and preferred nucleotides, A/T and G/C, were only found at the second and third nucleotides from both ends of the target site duplications, respectively, indicating that Tos17 has relatively low target-site specificity at the nucleotide sequence level. Integration targets were widely distributed over the chromosomes; however, preferential integration into the sucrose synthase 2 gene and into Tos17 itself was demonstrated by PCR screening using pooled DNA prepared from the mutant population. Hybridisation studies indicated that Tos17 preferentially integrates into low-copy-number regions of the genome. In agreement with this result, about 30% of flanking sequences examined showed significant homology to known genes. Taken together, these results show that Tos17 can have a significant impact on the rice genome and can be used as a tool for efficient insertional mutagenesis.

Binding Sites↗

Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells.

PURPOSE: This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I(Ca)) and membrane action potential in the bullfrog single atrial myocyte. METHODS: Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I(Ca), membrane resting potential, and action potential. RESULTS: Ketamine (10(-5)-10(-3) M) showed dose-dependent inhibition of I(Ca) in a reversible manner. The 50% inhibitory concentration (IC(50)) of ketamine on I(Ca) was estimated to be 0.92 x 10(-5) M. Use-dependent block of I(Ca) was not observed. The resting membrane potential was depolarized at a high concentration (10(-4) M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10(-4) M). CONCLUSION: Ketamine has an inhibitory effect on I(Ca) in the bullfrog single atrial myocyte, and a high dose (10(-4) M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I(Ca) seems to be a direct effect on the L-type calcium channel, not like an open channel blocker.

Journal Article↗

Effect of electrostatic interactions on phase stability of cubic phases of membranes of monoolein/dioleoylphosphatidic acid mixtures.

To elucidate effects of electrostatic interactions resulting from surface charges on structures and phase stability of cubic phases of lipid membranes, membranes of 1-monoolein (MO) and dioleoylphosphatidic acid (DOPA) (DOPA/MO membrane) mixtures have been investigated by small-angle x-ray scattering method. As increasing DOPA concentration in the DOPA/MO membrane at 30 wt% lipid concentration, a phase transition from Q(224) to Q(229) phase occurred at 0.6 mol% DOPA, and at and above 25 mol% DOPA, DOPA/MO membranes were in the L(alpha) phase. As NaCl concentration in the bulk phase increased, for 10% DOPA/90% MO membrane in excess water, a Q(229) to Q(224) phase transition occurred at 60 mM NaCl, and then a Q(224) to H(II) phase transition occurred at 1.2 M NaCl. Similarly, for 30% DOPA/70% MO membrane in excess water, at low NaCl concentrations it was in the L(alpha) phase, but at and above 0.50 M NaCl it was in the Q(224) phase, and then at 0.65 M NaCl a Q(224) to H(II) phase transition occurred. These results indicate that the electrostatic interactions in the membrane interface make the Q(229) phase more stable than the Q(224) phase, and that, at larger electrostatic interactions, the L(alpha) phase is more stable than the cubic phases (Q(224) and Q(229)). We have found that the addition of tetradecane to the MO membrane induced a Q(224)-to-H(II) phase transition and also that to the 30% DOPA/70% MO membrane induced an L(alpha)-to-H(II) phase transition. By using these membranes, the effect of the electrostatic interactions resulting from the membrane surface charge (DOPA) on the spontaneous curvature of the monolayer membrane has been investigated. The increase in DOPA concentration in the DOPA/MO membrane reduced the absolute value of spontaneous curvature of the membrane. In the 30% DOPA/70% MO membrane, the absolute value of spontaneous curvature of the membrane increased with an increase in NaCl concentration. On the basis of these new results, the phase stability of DOPA/MO membranes can be reasonably explained by the spontaneous curvature of the monolayer membrane and a curvature elastic energy of the membrane.

Glycerides↗

Measurement of serum digitoxin in patients by radioimmunoassay using specific antiserum.

INTRODUCTION: Digitoxin is used to treat patients with heart failure. METHODS: A radioimmunoassay procedure for the specific determination for digitoxin in serum was developed using the antiserum (antiserum (A)) raised against digitoxin 3'-hemisuccinate-BSA conjugate. RESULTS: The intra- and interassay variability were <10% in the range of 5-100 ng/ml. The specificities of antiserum (A) and the commercial anti-digitoxin antiserum (antiserum (B)) were assessed by cross-reactivity studies with various related compounds. Antiserum (A) was highly specific for digitoxin. Mean digitoxin concentrations in serum samples (n=34) from digitalized patients by RIA using these antisera were 10.0 and 12.4 ng/ml, respectively. CONCLUSION: This RIA using antiserum (A) measure unmetabolized digitoxin and may be applicable for pharmacokinetic studies.

Animals↗

Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemic patients.

Several studies have previously reported high levels of total tissue factor pathway inhibitor (TFPI) antigen in patients with hypercholesterolemia. The relationship between serum lipid concentrations and total and free-form TFPI antigen in 32 patients with primary type II hypercholesterolemia and 38 age- and gender-matched normolipemic control subjects was studied (Study Group I). Plasma concentrations of total TFPI (tTFPI) antigen, free-form TFPI (fTFPI) antigen, tissue factor antigen, factor VII activity (FVIIc), and prothrombin fragment 1+2 (F1+2) were measured. The median levels of tTFPI, fTFPI, FVIIc, and F1+2 were higher in hyperlipidemic patients compared with those in healthy subjects. The effect of lowering total cholesterol on hypercoagulability in 25 patients with type II hyperlipoproteinemia (Study Group II) were also studied. The median levels of tTFPI, FVIIc, and F1+2 decreased significantly after 6 months of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor therapy in the hypercholesterolemic patients. On the other hand, fTFPI did not change after therapy. Plasma tTFPI was strongly correlated with total cholesterol and low density lipoprotein (LDL)-cholesterol in hyperlipidemic patients. In contrast to the strong correlation between tTFPI and total cholesterol, the correlation between plasma fTFPI and total cholesterol was relatively poor. These results suggest that the activation of the anticoagulant system as well as the activation of the coagulation system may occur in association with hypercholesterolemia. Furthermore, the results of this study may suggest that lowering of total cholesterol in hyperlipidemic patients reduces the thrombin generation in plasma and that down-regulation of LDL does not affect the anticoagulant potency of TFPI in plasma.

Adult↗

The Lurcher mutation reveals Ca(2+) permeability and PKC modification of the GluRdelta channels.

The physiological function of the GluRdelta subfamily which is one of the glutamate receptor (GluR) channel subunits has not yet been clarified, because no GluR channel activity has been detected in heterologous expression systems. The Lurcher mutation, a point mutation of the GluRdelta2 subunit, converts it into a constitutively active and cation-permeating channel. We introduced this mutation into GluRdelta1 and GluRdelta2, AMPA-selective, and NMDA-selective GluR channel subunits, and characterized their channel properties. It was shown that the Lurcher mutation alters the gating properties of AMPA- and NMDA-selective GluR channels, but not their cation permeabilities nor metabolic modulations. These findings support the idea that the Lurcher mutant homomeric GluRdelta1 channels are permeable to Ca(2+) as do the mutant GluRdelta2 channels, reflecting their original channel properties. We also found that cation permeability of the mutant GluRdelta1 channels was decreased by TPA, a protein kinase C activator. It indicates the possibility that phosphorylation by PKC activation may inhibit channel with wild-type GluRdelta1 subunit.

Amino Acid Sequence↗

Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns.

To clarify the role of plasminogen activator inhibitor type 1 (PAI-1) in postburn hypercoagulation, we assayed the plasma levels of tissue-type plasminogen activator (t-PA) antigen, total PAI-1 antigen, and total t-PA-PAI-1 complex in 15 burned patients. The total body surface area of the burn injury ranged from 30 to 80%. Serial blood samples were collected from 12 to 168 h following the thermal injury. The plasma t-PA level and the free PAI-1 level increased significantly in the immediate postburn period, and the percent increase in the latter over the values in the healthy controls was much greater than that of the former. The ratio of the concentrations of t-PA-PAI-1 complex to free PAI-1 decreased throughout the 7 postburn days. The fact that the decreases in this ratio clearly showed no dissociation of the euglobulin fraction suggests that the postburn hypofibrinolysis occurred as a result of increased synthesis of PAI-1. On the other hand, changes in several parameters of the coagulation or fibrinolysis system and in plasma thrombomodulin showed that postburn hypercoagulability is associated with secondary hyperfibrinolysis with no evidence of vascular endothelial injury. The paradoxical coexistence of postburn hyper- and hypofibrinolysis is a good reflection of the character of PAI-1, which is a biphasic protein that is both a functional protein and an acute phase reactant. Thus, increased synthesis of PAI-1 may not enhance postburn hypercoagulability to create a coagulation-dominant type of disseminated intravascular coagulation severe enough to trigger multiple organ dysfunction syndrome. In conclusion, increased synthesis of PAI-1 in the initial postburn period reflects an integrated endothelial response to burn stress, and because it is a functional protein, the concentration of free PAI-1 antigen may be an important index for predicting secondary consumption coagulopathy.

Adult↗

Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor.

Chondrogenesis is an essential component of endochondral fracture healing, though the molecular and cellular events by which it is regulated have not been fully elucidated. In this study, we used a rat model of closed fracture healing to determine the spatial and temporal expression of genes for cartilage-specific collagens. Furthermore, to determine the effects of basic fibroblast growth factor (bFGF) on chondrogenesis in fracture healing, we injected 100 microg recombinant human bFGF into the fracture site immediately after fracture. In normal calluses, pro-alpha1(II) collagen mRNA (COL2A1) was detected in proliferative chondrocytes beginning on day 4 after the fracture, and pro-alpha1(X) collagen mRNA (COL10A1) in hypertrophic chondrocytes beginning on day 7. In FGF-injected calluses, the cartilage enlarged in size significantly. On day 14, both COL2A1- and COL10A1-expressing cells were more widely distributed, and the amounts of COL2A1 and COL10A1 mRNAs were both approximately 2-fold increased when compared with uninjected fractures. Temporal patterns of expression for these genes were, however, identical to those found in normal calluses. The number of proliferating cell nuclear antigen-positive cells was increased in the non-cartilaginous area in the bFGF-injected calluses by day 4. The present molecular analyses demonstrate that a single injection of bFGF enhances the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. However, maturation of chondrocytes and replacement of the cartilage by osseous tissue are not enhanced by exogenous bFGF, and this results in the prolonged cartilaginous callus phase. We conclude that, in the healing of closed fractures of long bones, exogenous bFGF has a capacity to enlarge the cartilaginous calluses, but not to induce more rapid healing.

Animals↗

Hepatocyte growth factor (HGF) activator expressed in hair follicles is involved in in vitro HGF-dependent hair follicle elongation.

Hepatocyte growth factor (HGF), a paracrine factor secreted by follicular papilla cells, acts on neighboring follicular epithelial cells to promote follicular growth, while HGF activator is a serine proteinase, which converts inactive single-chain HGF to the active heterodimeric form. In this study, using 3' rapid amplification of cDNA end/nested polymerase chain reaction (3' RACE/nested PCR) and immunoblotting, we confirmed the expression of HGF activator in both cultured human follicular papilla cells and outer root sheath cells. HGF activator mRNA was expressed in all of the isolated 15 anagen hair follicles taken from the scalps of seven individuals. In an organ culture system, single-chain HGF stimulated hair follicle elongation, which was partially inhibited by aprotinin, a serine proteinase inhibitor (P<0.01). These results suggest that single-chain HGF secreted from follicular papilla cells is converted to an active heterodimeric form by intrinsic HGF activator and that the resultant active form of HGF stimulates hair growth.

Cells, Cultured↗

Induction of tumor necrosis factor-alpha in solid tumor region by the orally administered synthetic muramyl dipeptide analogue, romurtide.

The novel applications of a muramyl dipeptide analogue, romurtide, were investigated. When mice were intravenously injected with 10-1000 micrograms/mouse of romurtide as a primer and 3 KE/mouse of OK-432 as a trigger, systemic tumor necrosis factor-alpha (TNF-alpha) activity was increased. Similar effects were also detected by oral administration of romurtide at 1000 to 10,000 micrograms/mouse. These effects reached maximum at 3 h (intravenous injection, i.v.) or 6 h (oral administration, p.o.) after administration and were sustained for 48 h. When romurtide was administered to MM46 tumor-bearing mice orally, the significant augmentation of TNF-alpha production could be detected in the solid tumor and the liver. When romurtide was intravenously injected to the tumor bearer, the TNF-alpha production was significantly augmented in the spleen. These findings suggest that romurtide can augment the host defense system by both the parenteral and oral route, and indicate the possibility of a new type of anti-tumor therapy to induce TNF-alpha in the tumor region.

Acetylmuramyl-Alanyl-Isoglutamine↗

Macrophage-oriented cytotoxic activity of novel triterpene saponins extracted from roots of Securidaca inappendiculata.

It is recognized that macrophages in peripheral tissues often proliferate under pathological conditions such as tumors, inflammation and atherosclerosis. Because the growth state of macrophages is believed to be a factor regulating the pathological process of the diseases, substances that regulate macrophage growth or survival may be useful for disease control. In this paper, we identified the activity inhibiting macrophage growth in a hot water extract of roots of Securidaca inappendiculata. The extract markedly inhibited macrophage colony-stimulating factor (M-CSF/CSF-1)-induced growth of macrophages, whereas it exerted a less potent effect on growth of Concanavalin A (Con A)-stimulated thymocytes or M-CSF-stimulated bone marrow cells. The inhibition of macrophage growth was caused by a cytotoxic effect rather than a cytostatic effect. Cell death was due to the induction of apoptosis, as judged by staining with terminal deoxynucleotidyl transferase-mediated d-UTP nick end labelling (TUNEL). The cytotoxic activity seemed to be specific to peripheral macrophages; it showed a weak effect on the growth and survival of tumor cell lines including a macrophage-like cell line, J-774.1. Moreover, the saponin fraction induced apoptotic cell death of macrophages only when they were stimulated by M-CSF; it did not affect the viability of macrophages cultured without M-CSF or with granulocyte/macrophage-CSF. We determined the structures of the two active triterpene saponin compounds in the fraction, named securioside A and securioside B having a 3,4-dimethoxycinnamic group which is essential for the cell death-inducing activity. They are believed to be the primary compounds of new drugs for the treatment of pathological states in which macrophage proliferation occurs.

Animals↗

Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat.

Recent experiments have shown that exogenous basic fibroblast growth factor (bFGF) enlarges fracture callus and accelerates the healing of osteotomized long bones. The actions of bFGF are mediated by four different transmembrane receptors (FGFR1-4). Among them, FGFR1 has a high affinity for bFGF, and gain-of-function mutations of the FGFR1 gene cause craniosynostosis in humans. Gene expression for FGFR1 has been analyzed in embryogenesis; however, in skeletal repair, detailed expression of FGFR1 has not been fully established. In the present study, a rat model of closed femoral fracture healing was used to quantify mRNA encoding the FGFR1 and to characterize cells expressing FGFR1 by in situ hybridization. Gene expression for FGFR1 was rapidly upregulated after fracture; its mRNA level on day 1 was 3.4-fold higher than that of unfractured femora. At this stage, a moderate signal for FGFR1 was detected in periosteal osteoprogenitor cells, inflammatory cells near fracture sites, and cells among muscle layers. FGFR1 mRNA reached peak expression when callus remodeling actively progressed (6.8-fold on day 14), and remained elevated even in the later stages of healing (6.3-fold on day 28). During the intermediate stage of fracture healing, a strong signal for FGFR1 was diffusely distributed in mature osteoblasts in the hard callus, and mature osteoclasts also expressed a weak signal for FGFR1. These results suggest that FGF/FGFR1 signaling has multifunctional roles during fracture healing and may regulate both osteoblasts and osteoclasts, contributing to bone formation and callus remodeling.

Animals↗