Biomedical subjects

E H Burger

Publications and source records attributed to E H Burger.

At least 55 records · Page 3Linked to original sources

PubMed2000

Correlation between ALK-6 (BMPR-IB) distribution and responsiveness to osteogenic protein-1 (BMP-7) in embryonic mouse bone rudiments.

Osteogenic protein-1 (OP-1) or bone morphogenetic protein-7 (BMP-7) stimulates cartilage formation in mouse bone rudiments in vitro but arrests terminal differentiation of prehypertrophic chondrocytes into hypertrophic chondrocytes. In this study we report that these effects of OP-1 depend on the developmental stage of the bone rudiment, early stages (E14 and E15 metatarsals) being most responsive. E17 metatarsals that already contained a hypertrophic area that had initiated mineralization were no longer affected by OP-1. We then investigated whether the sensitivity of the early long bone rudiments to OP-1 correlated with high expression of the OP-1 binding type I serine/threonine kinase receptors (activin receptor-like kinase: ALK-2/ActR-I, ALK-3/BMPR-IA or ALK-6/BMPR-IB) at this early stage. We did not find any significant difference in overall mRNA levels of these ALKs between stages E14 through E17 as assessed by RNase protection assays. However, by immunohistochemistry we found that ALK-6 staining was strong in E14 early cartilage primordium and its future perichondrium but dropped sharply to low levels in these cell types until onset of chondrocyte (pre)hypertrophy at E16. By contrast, ALK-2 and ALK-3 immunostainings in E14 were barely detectable. We also examined by immunohistochemistry the local synthesis of OP-1. OP-1 was present in E14 early chondrocytes and forming perichondrium but in low amounts; however, production of OP-1 increased in these cell types with age. All three receptor types as well as OP-1 were present in significant amounts in prehypertrophic chondrocytes and late hypertrophic chondrocytes including those undergoing mineralization. The temporary high immunostaining for ALK-6 in the early proliferating chondrocytes and future perichondrium of E14 bone rudiments, and its absence in older bones correlated with the sensitivity of chondrocytes and perichondrium to (exogenous) OP-1. We therefore propose that the effects of OP-1 on these cells in vitro are mediated by ALK-6/BMPR-IB. We furthermore conclude that locally produced OP-1 is a potential autocrine/paracrine growth factor. Increased local production of OP-1 may be partially responsible for the age-related decrease in responsiveness to exogenous OP-1 with respect to hypertrophy and mineralization of cartilage.

Activin Receptors↗

PubMed1999

Mineralization processes in demineralized bone matrix grafts in human maxillary sinus floor elevations.

For reconstruction of the severely resorbed lateral maxilla for dental implant placement, one of the successful procedures is to elevate the maxillary sinus floor by implanting demineralized bone matrix (DBM). We studied bone formation in DBM grafts in the lateral maxilla in humans by means of histology and histomorphometry. Six months after grafting, at the time of dental implantation biopsies were taken from the grafted areas of seven patients. All biopsies contained mineralized matrix (MM) in the grafted area. At close inspection, three types of mineralization were found. First, lamellar biomineralization was seen in and near the maxillary host bone. Second, remineralization was observed in some particles that probably had not been completely demineralized. In the area connecting the graft and host bone, where woven bone was formed against DBM particles, a third mechanism was detected. In this case many dotlike foci of remineralization appeared close to the bone-DBM interface. The remineralized DBM and woven bone were both subsequently remodeled. Bone formation was most active in the area adjoining the maxillary host bone. We conclude that in human sinus floor elevation, allogenic DBM increases mineralized tissue volume by osteoconduction that is supported by the remineralization processes. Osteoinduction by this material seems questionable.

Adult↗

PubMed1999

Why does intermittent hydrostatic pressure enhance the mineralization process in fetal cartilage?

The purpose of this study was to determine which factor is the most likely one to have stimulated the mineralization process in the in vitro experiments of Klein-Nulend et al. (Arth. Rheum., 29, 1002-1009, 1986), in which fetal cartilaginous metatarsals were externally loaded with an intermittent hydrostatic pressure, by compressing the gas phase above the culture medium. Analytical calculations excluded the possibility that the tissue was stimulated by changes in dissolved gas concentration, pH or temperature of the culture medium through compression of the gas phase. The organ culture experiments were also mechanically analyzed using a poroelastic finite element (FE) model of a partly mineralized metatarsal with compressible solid and fluid constituents. The results showed that distortional strains occurred in the region where mineralization proceeded. The value of this strain was, however, very sensitive to the value of the intrinsic compressibility modulus of the solid matrix (Ks). For realistic values of Ks the distortional strain was probably too small (about 2 microstrain) to have stimulated the mineralization. If the distortional strain was not the factor to have enhanced the mineralization process, then the only candidate variable left is the hydrostatic pressure itself. We hypothesize that the pressure may have created the physical environment enhancing the mineralization process. When hydrostatic pressure is applied, the balance of the chemical potential of water across cell membranes may be disturbed, and restored again by diffusion of ions until equilibrium is reached again. The diffusion of ions may have contributed to the mineralization process.

Animals↗

PubMed1999

The role of trabecular demineralized bone in combination with perichondrium in the generation of cartilage grafts.

The use of a composite graft of bovine trabecular demineralized bone matrix (DBM) and perichondrium has been found a reliable method for in vivo generation of cartilage. In the present study, the mechanism whereby this commercially available matrix increases cartilage formation was investigated. First, the time course of cartilage formation in vivo, in the combined implant of perichondrium and DBM in the rabbit ear was studied, with special focus on tissue reactions to DBM. DBM was colonized by macrophages from day 3 post-operatively, reaching a maximum after 2 weeks. Only a minimal number of neutrophils was found. After 3 weeks the DBM appeared to be resorbed. In the first week the DBM was invaded with chondroblasts, and chondrogenesis occurred between the first and second week of implantation. After 3 weeks, the initially formed islets of cartilage had fused. Next, the chondrogenic capacity of DBM itself was investigated by implantation of DBM without perichondrium. This never resulted in cartilage formation. Immunohistochemistry showed only a faint staining of the DBM for growth factors. This indicates a minimal chondrogenic effect of DBM alone and the requirement of perichondrium as cell provider. In order to define the conditions which cause chondrogenesis in composites of perichondrium and DBM, a series of in vitro culture experiments was performed in which the in vivo situation was mimicked step by step. The basic condition was perichondrium cultured in medium with 10% FCS. In this condition, cartilage formation was variable. Because in the in vivo situation both DBM and macrophages can release growth factors, the effect of IGF1, TGFbeta2 or OP1 added to the culture medium was tested. Neither the incidence nor the amount of cartilage formation was stimulated by addition of growth factors. Perichondrium wrapped around DBM in vitro gave cartilage formation in the perichondrium but the incidence and amount were not significantly stimulated compared to cultures of perichondrium without DBM. However, cartilage-like cells were found in the DBM suggesting an effect of DBM on perichondrium-derived cells. Finally, macrophages and/or blood were added to the composite DBM-perichondrium to mimic the in vivo situation as close as possible. However, no effect of this treatment was found. In conclusion, this study indicates that DBM itself has few chondrogenic qualities but functions merely as a spacer for cell ingrowth. The fast resorption of DBM by macrophages in vivo seems of importance for the cartilage forming process, but in vitro the presence of macrophages (in combination with blood) could not enhance chondrogenesis.

Animals↗

PubMed1999

Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide.

Bone morphogenetic protein-7, or BMP-7 (OP-1), is highly expressed in the perichondrium of embryonic long bones and is thought to play a role in endochondral ossification. Previously we have shown that BMP-7 inhibits terminal chondrocyte differentiation; that is, chondrocyte hypertrophy and mineralization in cultured explants of embryonic mouse metatarsals. However, the mechanism of this inhibition and the target cells of BMP-7 are still unknown. In this study we show that BMP-7 inhibits terminal chondrocyte differentiation indirectly, via an interaction with the periarticular region of the explants. This region also expresses parathyroid hormone-related peptide (PTHrP). PTHrP regulates terminal chondrocyte differentiation by inhibiting hypertrophic differentiation of prehypertrophic chondrocytes. The differentiating center in turn regulates PTHrP expression via a feedback loop involving Indian hedgehog (Ihh), which is expressed in the prehypertrophic chondrocytes. Ihh is thought to act on perichondrial cells, which in turn start to express an as yet unknown mediator that stimulates PTHrP expression in the periarticular region. It has been suggested that this factor belongs to the BMP-family. We investigated whether the inhibition of terminal chondrocyte differentiation by BMP-7 was due to upregulation of the PTHrP-Ihh feedback loop and whether BMP-7 was the unknown factor in the loop. Here we show that exogenous BMP-7 did not upregulate the mRNA expression of PTHrP, Ihh, or the PTH/PTHrP receptor in cultured wild-type embryonic metatarsals. Furthermore, BMP-7 could still inhibit terminal chondrocyte differentiation in the metatarsals of PTHrP-deficient (PTHrP-/-) mouse embryos. These data indicate that the BMP-7-mediated inhibition of terminal chondrocyte differentiation in vitro is independent of the PTHrP-Ihh feedback loop. We concluded that BMP-7 modulates terminal chondrocyte differentiation and cartilage mineralization of fetal bone explants in vitro via as yet unknown inhibitory factor(s) produced in the periarticular region.

Animals↗

PubMed1999

Histomorphometrical analysis of bone formed in human maxillary sinus floor elevations grafted with OP-1 device, demineralized bone matrix or autogenous bone. Comparison with non-grafted sites in a series of case reports.

Bone morphogenetic proteins have proven to be effective bone inductors in animals and are therefore promising as inductors of bone formation in humans. In the present study we investigated the tissue formed after grafting osteogenic protein 1 on a collagen carrier (OP-1-device) in the human sinus floor elevation procedure. Three patients were grafted with OP-1 device. For comparison 3 groups of 3 patients were included in the study receiving respectively, autogenous bone, human freeze-dried demineralized bone matrix (DBM) or no graft. This last group had a sufficient alveolar bone height for dental implantation. Six months after grafting, at the time of implantation, biopsies were taken from the grafted area and/or the future dental positions. Undecalcified sections were used for histological and histomorphometrical analysis. All grafted sinuses showed an increased osteoid percentage when compared to non-grafted sinuses. Autogenous bone grafts all showed lamellar bone formation. In the DBM grafts mostly woven bone had been formed, predominantly by what appeared to be osteo-conduction. The OP-1 device gave rise to bone formation in 2 of the 3 patients. After 6 months implants could only be placed in 1 out of the 3 patients treated with OP-1 device. This patient showed mature lamellar bone formation, comparable to autogenous bone grafts. In the second patient all bone found was woven and the presence of a high osteoid percentage and large osteocyte lacunae indicated that this was recently-formed bone. Remnants of the collagen carrier were rare and new bone was never found against them, suggesting that this bone was formed by osteo-induction. In the third patient no new bone had been formed. The device had been encapsulated with fibrous tissue and inflammatory reaction was present. We conclude that in the human sinus floor elevation OP-1 has potential bone inductive capacity, but that results in the 3 patients tested with the current OP-1 device are inconsistent.

Adult↗

PubMed1999

Histological observations of a bilateral maxillary sinus floor elevation 6 and 12 months after grafting with osteogenic protein-1 device.

OBJECTIVE: The purpose of this case study was to analyze the tissue formed in a maxillary sinus, 6 and 12 months after grafting with recombinant human osteogenic protein-1 (OP-1) linked to a collagen carrier of bovine origin. PATIENT AND METHODS: A 49-year-old woman referred for bilateral sinus floor elevation, was grafted with an OP-1 device. After 6 months, a biopsy was taken from one of the grafted areas. After 12 months, during implant placement, 5 biopsies were taken from the grafted area and the maxillary host bone. Biopsies were processed without decalcification for histological analyses. RESULTS: The biopsy taken after 6 months contained newly formed bone, fibrotic tissue and device remnants. After 12 months, however, bone was absent from all biopsies which were taken from the grafted area, while particles of the collagen carrier were still abundant. Inflammatory cells were observed between remnants of the collagen carrier in the grafted area. CONCLUSION: This study indicates that an onset of new bone formation, which was observed after 6 months, did not persist. 12 months after grafting no bone was present in the biopsies from the grafted area, while the collagen carrier had remained. Lack of mechanical loading, as a result of postponing implant placement from 6 to 12 months, may have resulted in resorption of the emerging bone which was present 6 months after grafting.

Biopsy↗

PubMed1999

Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes.

To maintain its structural competence, the skeleton adapts to changes in its mechanical environment. Osteocytes are generally considered the bone mechanosensory cells that translate mechanical signals into biochemical, bone metabolism-regulating stimuli necessary for the adaptive process. Prostaglandins are an important part of this mechanobiochemical signaling. We investigated the signal transduction pathways in osteocytes through which mechanical stress generates an acute release of prostaglandin E2 (PGE2). Isolated chicken osteocytes were subjected to 10 min of pulsating fluid flow (PFF; 0.7 +/- 0.03 Pa at 5 Hz), and PGE2 release was measured. Blockers of Ca2+ entry into the cell or Ca2+ release from internal stores markedly inhibited the PFF-induced PGE2 release, as did disruption of the actin cytoskeleton by cytochalasin B. Specific inhibitors of Ca2+-activated phospholipase C, protein kinase C, and phospholipase A2 also decreased PFF-induced PGE2 release. These results are consistent with the hypothesis that PFF raises intracellular Ca2+ by an enhanced entry through mechanosensitive ion channels in combination with Ca2+- and inositol trisphosphate (the product of phospholipase C)-induced Ca2+ release from intracellular stores. Ca2+ and protein kinase C then stimulate phospholipase A2 activity, arachidonic acid production, and ultimately PGE2 release.

Actins↗

PubMed1999

Responses of bone cells to biomechanical forces in vitro.

In this paper, we review recent studies of the mechanism by which mechanical loading of bone is transduced into cellular signals of bone adaptation. Current biomechanical theory and in vivo as well as in vitro experiments agree that the three-dimensional network of osteocytes and bone-lining cells provides the cellular basis for mechanosensing in bone, leading to adaptive bone (re)modeling. They also agree that flow of interstitial fluid through the lacunar-canalicular porosity of bone, as a result of mechanical loading, most likely provides the stimulus for mechanosensing, and informs the bone cellular network about the adequacy of the existing bone structure. Important signaling molecules involved in in vivo adaptive bone formation, as well as in in vitro cellular response to fluid flow, are nitric oxide and prostaglandins. The expression of key enzymes for nitric oxide and prostaglandin production in bone cells is altered by fluid shear stress in vitro. Together, these studies have increased our understanding of the cell biology underlying Wolff's Law. This may lead to new strategies for combating disuse-related osteoporosis, and may also be of use in understanding and predicting the long-term integration of bone-replacing implants.

Animals↗

PubMed1999

Mechanotransduction in bone--role of the lacuno-canalicular network.

The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Over the last several years significant progress has been made in this field, which we will try to summarize. These studies emphasize the role of osteocytes as the professional mechanosensory cells of bone, and the lacuno-canalicular porosity as the structure that mediates mechanosensing. Strain-derived flow of interstitial fluid through this porosity seems to mechanically activate the osteocytes, as well as ensuring transport of cell signaling molecules and nutrients and waste products. This concept allows an explanation of local bone gain and loss, as well as remodeling in response to fatigue damage, as processes supervised by mechanosensitive osteocytes.

Animals↗

PubMed1998

Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent.

Bone cells, in particular osteocytes, are extremely sensitive to shear stress, a phenomenon that may be related to mechanical adaptation of bone. In this study we examined whether human primary bone cells produce NO in response to fluid shear stress and established by RT/PCR which NOS isoforms were expressed before and after application of shear stress. One hour pulsating fluid flow (PFF; 0.7 +/- 0.02 Pa, 5 Hz) caused a rapid (within 5 min) 2 to 4-fold increase in NO production. NO release was only transiently increased during the first 15 min of exposure to PFF, and remained at control levels during a 1-24 hr postincubation period. In both control and PFF-treated cells, mRNA was easily detected for ecNOS, but not nNOS, and only minimal amounts iNOS were found. mRNA levels for ecNOS increased 2-fold at 1 hr after 1 hr PFF treatment. These results suggest that the rapid production of NO by human bone cells in response to fluid flow results from activation of ecNOS. PFF also leads to an increase in ecNOS mRNA which is likely related to the shear stress responsive element in the promoter of ecNOS.

Adaptation, Physiological↗

PubMed1998

Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro.

The objective of this study was to examine in vitro the influence of recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7)] on cartilage formation by human and goat perichondrium tissue containing progenitor cells with chondrogenic potential. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not added (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [35S]-sulphate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [35S]-sulphate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microg/mL (human explants: +148%; goat explants: +116%). Histology revealed that explants treated with 20-200 microg/mL of rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. It was concluded that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells in the stimulation of chondrocytic differentiation and production of cartilage matrix in vitro provides a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus rhOP-1 may promote early steps in the cascade of events leading to cartilage formation and could prove to be an interesting factor in the regeneration of cartilage in articular cartilage defects.

Animals↗

PubMed1998

Microgravity and bone cell mechanosensitivity.

Bone cells, in particular osteocytes, are extremely sensitive to mechanical stress, a quality that is probably linked to the process of mechanical adaptation (Wolff's law). The in vivo operating cell stress derived from bone loading is likely a flow of an interstitial fluid along the surface of the osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin synthesis and expression of inducible prostaglandin G/H synthase (PGHS-2 or inducible cyclooxygenase, COX-2), an enzyme that mediates the induction of bone formation by mechanical loading in vivo. Disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity has catabolic effects on the skeleton of astronauts, as well as on mineral metabolism in bone organ cultures. This might be explained simply as resulting from an exceptional form of disuse under weightlessness conditions. However, under microgravity conditions, the assembly of cytoskeletal elements may be altered, as gravity has been shown to determine the pattern of microtubular orientation assembled in vitro. Therefore, it is possible that the mechanosensitivity of bone cells is altered under microgravity conditions, and that this abnormal mechanosensation contributes to the disturbed bone metabolism observed in astronauts. In vitro experiments on the International Space Station should test this hypothesis experimentally.

Animals↗

PubMed1998

Stimulation of cartilage differentiation by osteogenic protein-1 in cultures of human perichondrium.

Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [&sup35;S]sulfate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [&sup35;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus, rhOP-1 may promote early steps in the cascade of events leading to cartilage formation. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.

Adolescent↗

PubMed1998

Response of normal and osteoporotic human bone cells to mechanical stress in vitro.

Bone adapts to mechanical stress, and bone cell cultures from animal origin have been shown to be highly sensitive to mechanical stress in vitro. In this study, we tested whether bone cell cultures from human bone biopsies respond to stress in a similar manner as animal bone cells and whether bone cells from osteoporotic patients respond similarly to nonosteoporotic donors. Bone cell cultures were obtained as outgrowth from collagenase-stripped trabecular bone fragments from 17 nonosteoporotic donors between 7 and 77 yr of age and from 6 osteoporotic donors between 42 and 72 yr of age. After passage, the cells were mechanically stressed by treatment with pulsating fluid flow (PFF; 0.7 +/- 0.03 Pa at 5 Hz for 1 h) to mimic the stress-driven flow of interstitial fluid through the bone canaliculi, which is likely the stimulus for mechanosensation in bone in vivo. Similar to earlier studies in rodent and chicken bone cells, the bone cells from nonosteoporotic donors responded to PFF with enhanced release of prostaglandin E2 (PGE2) and nitric oxide as well as a reduced release of transforming growth factor-beta (TGF-beta). The upregulation of PGE2 but not the other responses continued for 24 h after 1 h of PFF treatment. The bone cells from osteoporotic donors responded in a similar manner as the nonosteoporotic donors except for the long-term PGE2 release. The PFF-mediated upregulation of PGE2 release during 24 h of postincubation after 1 h of PFF was significantly reduced in osteoporotic patients compared with six age-matched controls as well as with the whole nonosteoporotic group. These results indicate that enhanced release of PGE2 and nitric oxide, as well as reduced release of TGF-beta, is a characteristic response of human bone cells to fluid shear stress, similar to animal bone cells. The results also suggest that bone cells from osteoporotic patients may be impaired in their long-term response to mechanical stress.

Adolescent↗

PubMed1998

Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development.

Bone morphogenetic proteins (BMPs) form a family of growth factors originally isolated from extracellular bone matrix that are capable of inducing bone formation ectopically. We studied the expression, tissue localization, and function of BMP-7 (OP-1) during tooth development in rodents. Patterns of BMP-7 gene expression and peptide distribution indicated that BMP-7 was present in dental epithelium during the dental lamina, bud, and cap stages. During the bell stage, BMP-7 mRNA expression and protein distribution shifted from dental epithelium toward the dental mesenchyme. With advancing differentiation of odontoblasts, BMP-7 protein staining in the dental papilla became restricted to the layer of fully functional odontoblasts in the process of depositing (pre)dentin. Secretory-stage ameloblasts exhibited weak immunostaining for BMP-7. A restricted pattern of staining in ameloblasts became apparent in post-secretory stages of amelogenesis. Also, cells of the forming periodontal ligament were immunopositive. Histological analysis of tooth development in neonatal BMP-7-deficient mice did not reveal obvious changes compared with wild-type mice. We conclude that, in developing dental tissues, BMP-7 has distribution and expression patterns similar to those of other BMP members but is not an essential growth factor for tooth development, possibly because of functional redundancy with other BMP members or related growth factors.

Ameloblasts↗

PubMed1998

[Guided bone regeneration for dental implantology].

Guided bone regeneration nowadays offers good possibilities to repair local bone defects. Membranes are used to cover the defects. There are many types available. The anatomy of the defect determines mainly which membrane type should be used or which surgical steps should be followed. Most difficult are the one-wall defects, less difficult are four-wall defects. Guided bone regeneration is predictable, but the procedure is technical sensitive and complications and contaminations will easy occur. All steps need to be done carefully, including patient selection and postoperative follow-up care. Implant insertion into the defect can be done simultaneously but will give a higher risk for complications. For this reason, care should be taken for regeneration procedures in aesthetic demanding areas.

Alveolar Process↗

PubMed1997

Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures.

We have shown earlier that mechanical stimulation by intermittent hydrostatic compression (IHC) promotes alkaline phosphatase and procollagen type I gene expression in calvarial bone cells. The bone matrix glycoprotein osteopontin (OPN) is considered to be important in bone matrix metabolism and cell-matrix interactions, but its role is unknown. Here we examined the effects of IHC (13 kPa) on OPN mRNA expression and synthesis in primary calvarial cell cultures and the osteoblast-like cell line MC3T3-E1. OPN mRNA expression declined during control culture of primary calvarial cells, but not MC3T3-E1 cells. IHC upregulated OPN mRNA expression in late released osteoblastic cell cultures, but not in early released osteoprogenitor-like cells. Also, in both proliferating and differentiating MC3T3-E1 cells, OPN mRNA expression and synthesis were enhanced by IHC, differentiating cells being more responsive than proliferating cells. These results suggest a role for OPN in the reaction of bone cells to mechanical stimuli. The severe loss of OPN expression in primary bone cells cultured without mechanical stimulation suggests that disuse conditions down-regulate the differentiated osteoblastic phenotype.

3T3 Cells↗