Biomedical subjects

W Hofstetter

Publications and source records attributed to W Hofstetter.

At least 19 recordsLinked to original sources

PubMed2003

Early osteoarthritic changes of human femoral head cartilage subsequent to femoro-acetabular impingement.

OBJECTIVE: To use the surgical samples of patients with femoro-acetabular impingement due to a nonspherical head to analyze tissue morphology and early cartilage changes in a mechanical model of hip osteoarthritis (OA). DESIGN: An aberrant nonspherical shape of the femoral head has been assumed to cause an abutment conflict (impingement mechanism) of the hip with subsequent cartilage lesions of the acetabular rim and surface alterations of the nonspherical portion of the head. In this study, 22 samples of the nonspherical portions of the head have been obtained during hip surgery from young adults (mean 30.4 years, range 19-45 years) with an impingement conflict. The samples were first compared with tissue from the same area obtained from six age-matched deceased persons (control group) with normal hip morphology and second with cartilage from 14 older patients with advanced OA. All samples were characterized histologically and hyaline cartilage was graded according to the Mankin criteria. They were further subjected to examination on a molecular basis by immunohistology for cartilage oligomeric matrix protein (COMP), tenascin-C and a collagenase cleavage product (COL2-3/4C(long)) and by in situ hybridization for collagen type I and collagen type II. RESULTS: All samples from the patient group revealed hyaline cartilage with degenerative signs. According to the Mankin criteria, the cartilage alterations were significantly different when compared with the control group (p=0.007) but were less distinct when compared with cartilage from patients with advanced OA (p=0.014). Positive staining and distribution pattern for COMP, tenascin-C and COL2-3/4C(long) showed similarities between the samples from the impingement group and osteoarthritic cartilage but they were distinctly different when compared with healthy cartilage. Levels of collagen I and II transcripts were upregulated in 6 and 10, respectively, of the 14 samples with OA and in 9 and 12, respectively, of the 22 samples from the impingement group. None of the samples from the control group showed upregulation of Collagen I and II mRNA. CONCLUSIONS: The aberrant nonspherical portion of the femoral head in young patients with an impingement conflict consists of hyaline cartilage which shows clear degenerative signs similar to the findings in osteoarthritic cartilage. The tissue alterations are distinctly different when compared with a control group, which substantiates an impingement conflict as an early mechanism for degeneration at the hip joint periphery.

Adult↗

PubMed2003

Cryopreservation with dimethyl sulfoxide sustains partially the biological function of osteochondral tissue.

The clinical routine use of bone allograft transplants dates back to the discovery that grafts devitalized by freezing bear a reduced antigenicity. Graft failures, caused by a host versus graft reaction, however, remain a clinical problem. Previous investigations on pancreatic islet allografts revealed improved survival and biological function when fast cryopreservation (-70 degrees C/min) was performed in the presence of dimethyl sulfoxide (DMSO). The aim of this study was to determine the effect of fast freezing using DMSO on the biological function of osteochondral tissues. Organ culture was performed with neonatal femora of mice, untreated, rapidly frozen (-70 degrees C/min) with DMSO, or frozen without DMSO. After the culture, tissue morphology, cellular proliferation, osteoblast function, osteoclasts, and the presence of antigen-presenting cells were investigated. In untreated control femora histology appeared normal and proliferating and collagen-synthesizing osteoblasts, osteoclasts, and B-cells and macrophages were present. In frozen femora (with and without DMSO) a disintegration of the periosteum and the epiphyseal growth plate were observed and no active osteoblasts could be detected. Osteoclasts were partially detached from the bone surface. Cell proliferation was fully blocked in femora frozen in the absence of DMSO, while freezing in the presence of DMSO preserved cell proliferation in the medullary canal. The proliferating cells do not express epitopes present on the cells of the B-cell or macrophage lineages. Although the biological function of osteoblasts and osteoclasts was lost upon freezing of osteochondral tissue, DMSO included in freezing protocols preserves some residual cell viability which may be of importance for early graft revascularization as has been previously demonstrated by our group.

Acid Phosphatase↗

PubMed2002

High-temperature superfluidity of fermionic atoms in optical lattices.

Fermionic atoms confined in a potential created by standing wave light can undergo a phase transition to a superfluid state at a dramatically increased transition temperature. Depending upon carefully controlled parameters, a transition to a superfluid state of Cooper pairs, antiferromagnetic states or d-wave pairing states can be induced and probed under realistic experimental conditions. We describe an atomic physics experiment that can provide critical insight into the origin of high-temperature superconductivity in cuprates.

Journal Article↗

PubMed2001

Kondo correlations and the Fano effect in closed Aharonov-Bohm interferometers.

We study the Fano-Kondo effect in a closed Aharonov-Bohm (AB) interferometer which contains a single-level quantum dot and predict a frequency doubling of the AB oscillations as a signature of Kondo-correlated states. Using the Keldysh formalism, the Friedel sum rule, and the numerical renormalization group, we calculate the exact zero-temperature linear conductance G as a function of the AB phase phi and level position epsilon. In the unitary limit, G(phi) reaches its maximum 2e(2)/h at phi = pi/2. We find a Fano-suppressed Kondo plateau for G(epsilon) similar to recent experiments.

Journal Article↗

PubMed2001

Development of transplanted fetal bones: differences between isografts and allografts in mice.

Allogeneic bone from bone banks frequently is used when large skeletal defects have to be bridged in orthopaedic surgery. Beside immunologic rejection of the graft, the loss in osteogenic potential caused by bone banking procedures may be a major reason for limited clinical success. Similar problems as described for bone have occurred with cartilage and osteochondral transplants. Improving the properties of allogenic bone so that its biologic activity becomes comparable to autologous bone could be substantially beneficial for the outcome of allograft transplantation. To dissect the steps involved in the integration of a fetal osteochondral graft as it matures to bone, the current study compared the development and biologic function of metatarsals from 18-day-old fetal mice freshly transplanted in three different immunologic settings. Morphologic assessment of (1) isografts and (2) allografts in nonsensitized hosts 12 days after transplantation revealed that the grafts bear an intrinsic potential to develop after transplantation. In allografts in nonsensitized hosts, however, a slight alteration in biologic activity as compared with isografts could be detected already in this early phase after transplantation by in situ hybridization for messenger ribonucleic acids encoding extracellular matrix proteins. (3) In contrast to isografts and allografts in nonsensitized hosts, morphologic features and biologic function of allografts transplanted to presensitized hosts were altered severely.

Acid Phosphatase↗

PubMed2000

Generalized numerical renormalization group for dynamical quantities

In this paper we introduce a new approach for calculating dynamical properties within the numerical renormalization group. It is demonstrated that the method previously used fails for the Anderson impurity in a magnetic field due to the absence of energy scale separation. The problem is solved by evaluating the Green function with respect to the reduced density matrix of the full system, leading to accurate spectra in agreement with the static magnetization. The new procedure provides a unifying framework for calculating dynamics at any temperature and represents the correct extension of Wilson's original thermodynamic calculation.

Journal Article↗

PubMed2000

Anderson impurity in a correlated conduction band

We investigate the physics of a magnetic impurity with spin 1/2 in a correlated metallic host. Describing the band by a Hubbard Hamiltonian, the problem is analyzed using dynamical mean-field theory in combination with Wilson's nonperturbative numerical renormalization group. We present results for the single-particle density of states and the dynamical spin susceptibility at zero temperature. New spectral features (side peaks) are found which should be observable experimentally. In addition, we find a general enhancement of the Kondo scale due to correlations. Nevertheless, in the metallic phase, the Kondo scale always vanishes exponentially in the limit of small hybridization.

Journal Article↗

PubMed2000

Transcriptional regulation of the expression of macrophage colony stimulating factor.

The regulatory regions for transcriptional control of the MCSF gene are unknown. We examined regulatory control in a 774-bp murine MCSF promoter transfected into MC3T3-E1 osteoblast-like and COS-7 cells. Deletion of upstream sequence from -635 increased basal activity of the promoter by at least four-fold, an increase that was maintained when PU.1, NFkappaB and Egr1/Sp1 consensus sequences were subsequently removed. Mutagenesis identified a suppressor element between -635 and -642 from the transcriptional start site and an oligonucleotide representing this sequence was retarded by nuclear cell protein. TNFalpha (1 ng/ml), PTH (5x10(-8) M), and IL-1alpha (100 pg/ml), which increased MCSF protein secretion, failed to enhance the transcriptional rate of the full-length promoter. TNFalpha was able to stimulate transcription of a heterologous reporter transfected into COS-7 containing multiple copies of the murine MCSF NFkappaB site inserted before a minimal promoter. In contrast, deletion of the same NFkappaB response element increased basal activity in the native promoter. Thus, the NFkappaB sequence may act as a negative regulator in the context of the endogenous promoter. Our results indicate that constitutive transcriptional activity conferred by the MCSF promoter may be damped by a suppressor protein. Transcriptional regulation, however, does not appear to be a major stimulatory mechanism for MCSF secretion.

3T3 Cells↗

PubMed2000

Abdominal insufflation does not cause hematogenous spread of colon cancer.

BACKGROUND AND PURPOSE: Previous investigators have suggested that port-site recurrences are possibly a result of abdominal insufflation, forcing viable cancer cells into the circulation to metastasize and thrive in areas of trauma. Using a syngeneic animal cancer model, we tested the hypothesis that pneumoperitoneum increases the incidence of wound metastasis by a blood-borne mechanism. METHODS: Male BD IX rats (N = 150) were injected intraperitoneally with 2 x 10(5) viable syngeneic 1,2-dimethylhydralazine-induced colon cancer cells (DHD-K12). Animals were divided into three groups: A (abdominal insufflation with 3-cm incision on the back into muscle remote from the peritoneum); B (3-cm back incision alone); and C (control group with 3-cm midline abdominal incision). Three weeks after surgery, the animals were euthanized and autopsied. RESULTS: In the two groups with back wounds, the incidence of cancer growth at the incision was zero, as demonstrated grossly and by histologic sample (A: 0/47, B: 0/43). In contrast, the autopsied control group had a 42% incidence of metastasis to the wound (25/59). There seemed to be no difference in the distribution of intra-abdominal disease between those rats that underwent insufflation and those that did not. CONCLUSION: It is unlikely that pneumoperitoneum promotes hematogenous wound implantation of free intraperitoneal cancer cells.

Animals↗

PubMed1999

In vivo expression of transcripts encoding the Glvr-1 phosphate transporter/retrovirus receptor during bone development.

In vitro observations suggest that inorganic phosphate (Pi) transport plays an important functional role in osteogenic cells and in their matrix vesicles for the initiation of matrix calcification. Recent studies have shown that the type III sodium-dependent Pi transporters, Glvr-1 and Glvr-2, are expressed in human osteoblast-like cells and have suggested a potential role for type III transporters in regulated Pi handling in osteogenic cells. To address the relevance of these findings in the context of bone formation in vivo and, in particular, in relation to matrix calcification, we investigated expression of the Glvr-1 transporter by in situ hybridization in developing embryonic murine metatarsals, using human Glvr-1 cDNA as a probe. In this model of endochondral ossification, expression of transcripts encoding Glvr-1 could be detected from day 17 of embryonic development. A hybridization signal for Glvr-1 was specifically observed in a subset of hypertrophic chondrocytes and could not be detected in osteoblasts. The expression of Glvr-1 mRNA was compared with that of transcripts encoding extracellular matrix proteins. Glvr-1 mRNA expression was confined to a population of early hypertrophic chondrocytes expressing type X collagen and to slightly more mature cells that express transcripts encoding osteopontin but lack type X collagen mRNA. No Glvr-1 transcripts were detected in fully differentiated hypertrophic chondrocytes. This pattern of Glvr-1 mRNA expression was maintained throughout embryonic development until after birth. In conclusion, the Glvr-1 phosphate transporter is selectively expressed in a subset of hypertrophic chondrocytes during endochondral bone formation, in a region where matrix mineralization proceeds. This observation represents the first in vivo evidence consistent with a potential role for this phosphate transporter in matrix calcification.

Animals↗

PubMed1998

Expression of colony-stimulating factor-1 in vivo during the formation of osteoclasts.

Colony-stimulating factor-1 (CSF-1), originally described as a growth factor for macrophages, is essential for the proliferation and differentiation of the cells of the osteoclast lineage. The cytokine is synthesized either as a secreted or a membrane-bound protein, which are encoded by four transcripts. The aim of the present study was to investigate the expression of CSF-1 in vivo at the mRNA level. Transcripts encoding CSF-1 were determined in total RNA from fetal murine metatarsals of different ages by a quantitative reverse-transcription polymerase chain reaction assay. Within the investigated period of time, the bone rudiments contain cells of the osteoclastic lineage representing well-defined differentiation stages. We found that only low levels of transcripts encoding CSF-1 could be detected in metatarsals from 15-day-old fetuses. Transcript levels increased slowly during the following days to reach a maximum in the rudiments from 18-day-old fetuses. After birth, in newborn animals, transcript levels were lowered again. While in rudiments from 15-day-old fetuses a considerable portion of the transcripts encoded the membrane-bound molecule, a transcript encoding the secreted form of the cytokine was the predominant species during the following days. These results suggest that the maintenance of proliferating and postmitotic osteoclast precursors requires low levels of CSF-1 only. Highest levels of locally synthesized CSF-1 are required, however, during the initial recruitment and activation of osteoclasts. After birth, levels of CSF-1 transcripts decrease again, suggesting that newly synthesized CSF-1 may be replaced by protein released from the mineralized matrix during resorption. In conclusion, the present data further strengthen the notion that CSF-1 produced locally acts in a paracrine fashion during the formation of osteoclasts.

Animals↗

PubMed1997

Role of CSF-1 in bone and bone marrow development.

There is a close interaction between the processes involved in osteogenesis and hemopoiesis. In developing bone, the osteoclasts, cells of hemopoietic origin, resorb and invade the calcified cartilage rudiment. As a result, the primitive marrow cavity is formed and hemopoiesis initiates. Osteogenic cells-osteoblasts and osteocytes-control the development and activity of the osteoclasts through the local release of factors. One factor responsible for this osteoblast-osteoclast interaction is colony-stimulating factor-1 (CSF-1). Studies performed on the osteopetrotic op/op mouse mutant have established that this factor is essential for proliferation and differentiation of the osteoclasts. Expression of CSF-1 receptors by mature osteoclasts and osteoclast precursors strongly suggests that CSF-1 action is exerted directly on cells of this lineage. In vivo, CSF-1 synthesis by osteoblasts is temporally and spatially related to sites of osteoclast development. Thus CSF-1 may represent one of the factors responsible for coupling hemopoiesis to osteogenesis. In vitro, osteoblasts express at least 4 transcripts encoding either a secreted or a membrane-bound form of CSF-1. At the protein level, osteoblasts in vitro synthesize the membrane-bound form and secrete the majority of CSF-1 as a proteoglycan, a small fraction of which is integrated into the matrix. These different molecular forms may locally restrict the biological action of this cytokine. Indeed, injection of recombinant human CSF-1 in op/ op mutants does not correct the osteoclast deficiency in the metaphyseal spongiosa of long bones, and sclerosis persists at this site. Similarly, the deficiency of some tissue macrophage populations in op/op mice is only partially or not at all corrected by injection of CSF-1. The expression of CSF-1 receptors by mature osteoclasts may imply that CSF-1 also influences their bone resorbing activity. Indeed, CSF-1 has been shown to induce osteoclast fusion, spreading, and survival. These findings suggest that CSF-1 is essential for the proliferation, differentiation, activity, and survival of tissue macrophages and osteoclasts, cells involved in tissue turnover. Furthermore, they corroborate the view that both osteoclasts and tissue macrophages stem from a CSF-1-dependent common precursor along the macrophage lineage.

Animals↗

PubMed1997

Identification and characterization of the insulin-like growth factor I receptor in mature rabbit osteoclasts.

In this study, the insulin-like growth factor I (IGF-I) receptor was identified in rabbit osteoclasts at mRNA and protein levels by in situ hybridization and autoradiography, respectively. Using highly purified mature osteoclasts, the IGF-I receptor was characterized on the molecular level according to its size and its affinity and number per osteoclast by isolation of the receptor-ligand complex and by binding studies, respectively, and on the cellular level according to the response of mature osteoclasts to IGF-I stimulation. In situ hybridization and autoradiography experiments showed that osteoclasts express IGF-I receptor mRNA and IGF-I binding sites. Chemical cross-linking of 125I-IGF-I bound to the purified mature osteoclasts and subsequent sodium dodecyl sulfide-polyacrylamide gel electrophoresis revealed the specific binding of 125I-IGF-I in complexes with molecular masses of 130 and 230-RD consistent with binding to the IGF-I receptor. In competition experiments, 125I-IGF-I binding to mature osteoclasts was dose-dependently reduced by unlabeled IGF-I in the picomolar range, whereas 20 nM insulin did not reduce the binding of 125I-IGF-I binding. The calculated receptor number was 6000 per osteoclast, and the Kd was 0.10 nM. Searching for a role of the IGF-I receptor in mature osteoclasts, we found no significant influence of IGF-I on the levels of the proform of matrix metaloproteinase 9 and tartrate-resistant acid phosphatase. However, the induction of nuclear fragmentation in serum-depleted cultures of purified mature osteoclasts was dose-dependently inhibited by IGF-I in the picomolar range, but not by 1 nM insulin. These data show that functionally active IGF-I receptor is present in mature osteoclasts.

Animals↗

PubMed1997

Macrophage colony stimulating factor down-regulates MCSF-receptor expression and entry of progenitors into the osteoclast lineage.

Macrophage colony-stimulating factor (MCSF), although necessary for entry of precursors into the early preosteoclast pathway, inhibits osteoclastogenesis at high doses. To clarify the relationship between MCSF and osteoclast formation, we investigated the effect of exogenous MCSF in murine bone marrow culture. Precursor proliferation and the expression of MCSF-receptor were examined after 4 days of culture in the presence or absence of accessory stromal cells. In both mixed marrow and destromalized cell cultures, exogenous MCSF dose-dependently decreased 125I-MCSF binding (by 65 +/- 5.0% at 3500 and 87 +/- 16.7% at-7000 U/ml, respectively) while enhancing mononuclear cell proliferation after 3 days of exposure (by 2.8- and 6.3-fold, respectively). These effects were maintained 24 h after removal of exogenous MCSF and, as such, likely represented an MCSF-induced change in MCSF receptor-bearing cells. Exposure to exogenous MCSF (3500 U/ml) days 2-4 dose-dependently inhibited tartrate resistant acid phosphatase positive multinuclear cell (TRAP+ MNC) formation counted at the end of day 7, by 64.3 +/- 4.1%. This inhibition of TRAP+ MNC formation was preceded by a 92 +/- 9% decrease in the expression of carbonic anhydrase II mRNA measurable at 4 days. These results indicate that MCSF promotes proliferation of a population of cells expressing lower cognate receptor sites. Changes in MCSF-receptor expression appear to modulate the final lineage selection of the pluripotent monoblastic progenitor.

Animals↗

PubMed1996

Synthesis of membrane- and matrix-bound colony-stimulating factor-1 by cultured osteoblasts.

Colony-stimulating factor-1 (CSF-1) is synthesized as a secreted or membrane-bound molecule. We investigated whether osteoblastic cells produce these forms of CSF-1. Glutaraldehyde-fixed cell layers supported proliferation of the macrophage cell line BAC1.2F5, suggesting the presence of membrane- or/and matrix-associated CSF-1. Furthermore, CSF-1 activity could be either extracted from the matrix or released from the cell membrane. A neutralizing antiserum against CSF-1 inhibited these activities. After labeling the cellular proteins with [35S] met/cys or [35S] SO4(2-), CSF-1 was immunoprecipitated and analyzed by SDS-PAGE. Under nonreducing conditions, bands with MW more than 200, 200, 100, and 50 kd were detected. These bands shifted to lower MW under reducing conditions. Treatment with chondroitin lyase ABC decreased the MW of the 200 kd monomer, proving the proteoglycan structure. Much smaller quantities of CSF-1 were found in the matrix extract than in the conditioned medium. Transforming growth factor beta (TGF-beta) increased both the synthesis of CSF-1 and its accumulation in the matrix. CSF-1 released with trypsin from the membrane fraction yielded on SDS-PAGE a band with MW of 60 and 30 kd under nonreducing and reducing conditions, respectively. Transcripts encoding both the secreted and the membrane-associated forms of the cytokine were detected in osteoblasts by reverse transcription polymerase chain reaction. These data indicate that osteoblastic cells produce the secreted forms, either remaining in the culture supernatant, or being associated to the matrix, and the membrane associated form of CSF-1.

Animals↗

PubMed1996

Expression of matrix proteins during the development of mineralized tissues.

The specific properties of mineralized tissues are defined by the composition of the fraction of the noncollagenous matrix proteins. Because these proteins play a pivotal role in the processes of cell differentiation and activation and of mineralization, their temporal and spatial expression is tightly regulated. Within this study, the expression of the enamel protein amelogenin and of the bone matrix proteins osteopontin, bone sialoprotein, osteocalcin, and osteonectin was investigated by in situ hybridization. Two models that allow observation of the formation of mineralized tissues were chosen. The development of bone and cartilage was observed on murine metatarsals from 15-day-old embryos up to 1-day-old mice. This time covers the periods of initial bone formation as well as onset of resorption of mineralized cartilage and bone. To study gene expression in the mineralized tissues of the dental organ, enamel, dentin, and cementum, developing molars ranging in age from 16-day-old embryos to 14 days after delivery were chosen. Within this time frame, the molars develop from an immature state to the differentiated organ which erupts through the mandibular bone. In the developing metatarsals, osteopontin and bone sialoprotein mRNAs were detected in osteoblasts and hypertrophic chondrocytes at the onset of mineralization. In the tooth organ, only cementoblasts expressed transcripts encoding the two proteins; odontoblasts and ameloblasts did not express these genes. Osteonectin was expressed by osteoblasts and hypertrophic chondrocytes as well, whereas in the molars it was produced exclusively by odontoblasts. Osteocalcin was expressed specifically by osteoblasts in the developing metatarsals. In tooth, osteocalcin transcripts were detected in odontoblasts. Finally, amelogenin was a specific product of ameloblasts. Thus, a sequential and cell type-restricted expression of matrix proteins takes place during the development of the mineralized tissues. The expression patterns of the transcripts encoding the bone matrix proteins suggest different biological roles depending on the time and site of expression.

Amelogenin↗

PubMed1996

Recent developments in the understanding of the pathophysiology of osteopetrosis.

Osteopetrosis is a rare metabolic bone disease characterized by a generalized increase in skeletal mass. It is inherited in a number of mammalian species, including man, and results from a congenital defect in the development or function of the osteoclasts. The consequent impairment of bone resorption prevents formation of bone marrow cavities, causes delayed or absent tooth eruption and results often in abnormally shaped bone. The pathogenetic defect may be intrinsic either to the osteoclast lineage or to the mesenchymal cells that constitute the microenvironment supporting the development and activation of the osteoclasts. In the first example, the disease can be cured by transplantation of hemopoietic cells. In some cases, bone marrow transplantation has also been successful in curing human osteopetrosis. This, together with the variability in the age of onset and severity of clinical aspects, suggests that a multiplicity of genetic mutations may cause the human disease. In recent years the genetic effects of some osteopetrotic mutations have been identified. This new information has been essential for the understanding of osteoclast biology. Colony stimulating factor 1 (CSF-1), the growth factor for cells of the mononuclear phagocytic system, is also essential for the development of osteoclasts. In the osteopetrotic (op) mouse, no biologically active CSF-1 is synthesized due to a point mutation in the coding region of its gene. This leads to an almost complete lack of osteoclast development and to impaired bone resorption. Altered CSF-1 production seems also to be involved in the toothless (tl) rat osteopetrosis. Recently, the mutation responsible for the microphthalmic (mi) mouse osteopetrosis has been identified in the gene encoding a member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors. The mi gene product seems to play a role in the fusion process of osteoclast precursor cells. Finally, osteopetrosis has been the result of experimental gene disruption in mice. Targeted disruption of the c-src proto-oncogene encoding a nonreceptor tyrosine kinase leads to a form of osteopetrosis where osteoclasts are present but inactive. This indicates that pp60c-src, localized primarily on ruffled border membranes and vacuoles of the osteoclasts, is important for osteoclastic function. Disruption of the c-fos proto-oncogene, a major component of the AP-1 transcription factor complex, leads to an osteopetrotic phenotype characterized by a complete absence of osteoclasts. The defect is intrinsic to hemopoietic precursors that are unable to progress beyond an early stage of osteoclast differentiation. In humans, deficiency of carbonic anhydrase II has been identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. A lack of expression of the vacuolar proton pump has been observed in osteoclasts of a patient with craniometaphyseal dysplasia. In conclusion, the disease, although rare, is of great pathophysiological relevance for our understanding of the processes that govern the development and function of osteoclasts.

Animals↗

PubMed1995

Downregulation of colony-stimulating factor-1 (CSF-1) binding by CSF-1 in isolated osteoclasts.

Colony-stimulating factor-1 (CSF-1), also called macrophage colony-stimulating factor, is the growth factor for the cells of the mononuclear phagocytic system. Furthermore, CSF-1 is essential in osteoclastogenesis and also affects mature osteoclasts. The receptor for CSF-1 was demonstrated on cells of the osteoclast lineage, with highest levels on the mature cells. This study investigated whether the binding of CSF-1 to isolated rat osteoclasts is modulated by the growth factor itself. Exposure of osteoclasts to CSF-1 for 1 hour virtually abolished binding of the growth factor. After removal of CSF-1, binding sites were restored within 4 hours. This recovery was blocked by cycloheximide, indicating the dependence on new protein synthesis for reexpression of receptors on the cell surface. The observed downregulation of CSF-1 binding sites might be a mechanism to control the effects of the growth factor on mature osteoclasts.

Animals↗