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Biomedical subjects

D Heymann

Publications and source records attributed to D Heymann.

At least 37 records · Page 2Linked to original sources
PubMed2001

[In vitro assessment of combining osteogenic cells with macroporous calcium-phosphate ceramics].

PURPOSE OF THE STUDY: Bone grafts or bone substitutes are required to fill bone defects resulting from trauma or surgical resection of tumors. Calcium-phosphate ceramics are synthetic bone substitutes which promote new bone formation by osteoconduction. These ceramics possess osteoconductive properties but have no intrinsic osteoinductive capacity. They are unable to induce new bone formation in extraossesous sites. One solution to develop bone substitutes with osteogenic properties would be to associate biomaterials with osteoprogenitors. MATERIALS AND METHODS: We studied the in vitro osteogenic potential of human bone-marrow cells cultured on macroporous calcium phosphate (CaP) ceramic, examining stromal cell proliferation and differentiation. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and immunological characterization of the extracellular fibrillar matrix formed by these cells. The specimens were examined by scanning and transmission electron microscopy. RESULTS: Human bone-marrow cells proliferated on CaP ceramic. The proliferating bone-marrow cells expressed an osteoblastic phenotype as shown by alkaline phosphatase activity and synthesis in ceramic pores of an extracellular matrix composed of fibronectin, osteocalcin and collagen I. In addition, numerous microcrystals of apatite precipitated on the fibrillar matrix, producing a mineralized fibrillar network within the ceramic. CONCLUSION: This study demonstrates that human bone-marrow cells cultured on macroporous CaP ceramic do not lose their osteoblastic phenotype even after 21 days of culture, and that they can induce osteogenesis in a CaP ceramic in vitro. This type of new "hybrid material" appears promising for the future.

Bone Marrow Cells↗
PubMed2001

Influence of bone environment on ceramic osteointegration in spinal fusion: comparison of bone-poor and bone-rich sites.

Quantitative experimental data showed differences in bone quality and ceramic incorporation between bone-rich and bone-poor implantation sites. Bone in-growth was significantly lower for ceramic implanted at a lumbar intertransverse than a laminar site. Bone-marrow enrichment of the lumbar intertransverse site (regarded as bone-poor) greatly facilitated ceramic osteointegration. The vertebral interbody site, despite theoretical richness in osteogenic precursor cells, might be bone-poor at the time of grafting as compared to the reference iliac crest site. These data have important clinical implications concerning the potential benefit of enriching both bone-poor and bone-rich sites.

Bone Marrow Transplantation↗
PubMed2001

Ultrastructural evidence in vitro of osteoclast-induced degradation of calcium phosphate ceramic by simultaneous resorption and phagocytosis mechanisms.

Osteoclasts are physiological polykaryons specialized in the resorption of calcified tissue. In the context of the clinical use of calcium-phosphate (CaP) ceramics as bone substitutes, this study used transmission electron microscopy to investigate the in vitro mechanisms of CaP ceramic degradation by osteoclastic cell types. Osteoclasts cultured on CaP ceramic developed typical ultrastructural features of bone osteoclasts, such as a polarized dome shape, a clear zone and a ruffled border. Modification of the shape and density of CaP crystals under the ruffled border indicated an acidic microenvironment. Moreover, osteoclasts were able to degrade ceramic by simultaneous resorption and phagocytosis mechanisms. Phagocytosis did not alter the ability of osteoclasts to resorb CaP ceramic. The phagocytosis mechanism consisted of three steps: crystal phagocytosis, disappearance of the endophagosome envelope membrane and fragmentation of phagocytosed crystals within the cytoplasm. The common mechanism of phagocytosis described here is similar to that observed with the monocyte/macrophage lineage, confirming that osteoclasts are part of the mononuclear phagocyte system. Osteoclasts are thus clearly involved in CaP degradation by means of resorption and phagocytosis.

Animals↗
PubMed2001

Potential synergies between matrix proteins and soluble factors on resorption and proteinase activities of rabbit bone cells.

Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-alphavbeta3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by alphavbeta3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with alphavbeta3 integrin, by another adhesion molecule.

Animals↗
PubMed2001

Scanning electron microscopic description of cellular activity and mineral changes in feline odontoclastic resorptive lesions.

The cellular activity and changes in mineral composition of dental tissues involved in feline odontoclastic resorptive lesions were investigated. Teeth with at least 1 lesion (n = 10) were extracted from 10 different cats that were presented primarily for chronic gingivostomatitis and/or severe periodontal disease. Scanning electron microscopic methods were used to determine the presence of resorptive cells in 8 teeth while 2 teeth were evaluated for pathologic changes in dental mineral composition. Observations were complicated by the presence of organic wear on the dental surfaces, however resorptive cells could be clearly identified in feline odontoclastic resorptive lesions. Resorptive cells had morphologic features indicative of "osteoclast-like" cells or odontoclasts. Resorptive cell activity created a resorption area of darker dentin continuous with physiologic dentin. The darker dentin area seemed poorly mineralized and showed a significantly lower calcium/phosphorous ratio compared with adjacent physiologic denting in 1 tooth. A significantly higher level of magnesium combined with available carbonate ions may have increased the solubility in areas of darker dentin.

Animals↗
PubMed2000

Cysteine protease production by human osteosarcoma cells (MG63, SAOS2) and its modulation by soluble factors.

The production of cysteine protease by two human osteosarcoma cell lines (MG-63 and SaOS2) was analyzed, as well as their modulation by interleukin 1beta (hIL-1 beta), interleukin 6 (hIL-6), insulin growth factor-1 (hIGF-1), oncostatin M (hOSM), leukemia inhibitory factor (hLIF) and growth hormone (hGH). Cysteine protease activities were detected using a synthetic substrate. The protease activities (especially cathepsin L activity) of both cell lines were increased significantly in the presence of hIL-1 beta, hIL-6 and hOSM. In contrast, hIGF-1 and hGH decreased these activities, and no effect was detectable in the presence of hLIF. The addition of antibodies against the gp-130 chain of the hIL-6 and hOSM receptors totally inhibited the stimulating effect of these two cytokines on cysteine protease activities. In increasing collagen type I degradation, hIL-1beta, hIL-6 and hOSM could be involved in bone resorption, whereas the inhibitory action of hIGF-1 and hGH on collagen type I degradation suggest that this factor could play a role in bone formation.

Cathepsin B↗
PubMed2000

gp130 Cytokine family and bone cells.

Bone tissue is continually being remodelled according to physiological circumstances. Two main cell populations (osteoblasts and osteoclasts) are involved in this process, and cellular activities (including cell differentiation) are modulated by hormones, cytokines and growth factors. Within the last 20 years, many factors involved in bone tissue metabolism have been found to be closely related to the inflammatory process. More recently, a cytokine family sharing a common signal transducer (gp130) had been identified, which appears to be a key factor in bone remodelling. This family includes interleukin 6, interleukin 11, oncostatin M, leukaemia inhibitory factor, ciliary neurotrophic factor and cardiotrophin-1. This paper provides an exhaustive review of recent knowledge on the involvement of gp130 cytokine family in bone cell (osteoblast, osteoclast, etc.) differentiation/activation and in osteoarticular pathologies.

Animals↗
PubMed2000

Modulation by soluble factors of gelatinase activities released by osteoblastic cells.

This study investigated the ability of normal human osteoblasts (hOb) and osteogenic sarcoma cells (MG-63 and SaOS2) to produce gelatinases and undergo modulation by interleukin 1beta (IL-1beta), interleukin 6 (IL-6), oncostatin M (OSM), leukaemia inhibitory factor (LIF), growth hormone (GH) and insulin-like growth factor-I (IGF-I). Gelatinase activities were determined by zymogaphy, and a quantitative analysis was performed by ELISA. The MMP-2 activities of the three cell lines were significantly increased in the presence of IL-1beta and IL-6, but no modulation of MMP-2 activities was observed in the presence of OSM, LIF and GH. IGF-I increased the activity released by SaOS2 and hOb, but no modulation was detectable in MG-63 cell conditioned medium. An upmodulation of pro-MMP-2 secretion by SaOS2 and hOb was observed for all soluble factors used, whereas an upmodulation of pro-MMP-2 secretion by MG-63 was observed only in the presence of IL-1beta, IL-6 and IGF-I. Thus, osteoblastic cells modulated by cytokines can be involved in bone resorption as a result of the protease activities released.

Cells, Cultured↗
PubMed2000

Public health implications of emerging zoonoses.

Many new, emerging and re-emerging diseases of humans are caused by pathogens which originate from animals or products of animal origin. A wide variety of animal species, both domestic and wild, act as reservoirs for these pathogens, which may be viruses, bacteria or parasites. Given the extensive distribution of the animal species affected, the effective surveillance, prevention and control of zoonotic diseases pose a significant challenge. The authors describe the direct and indirect implications for public health of emerging zoonoses. Direct implications are defined as the consequences for human health in terms of morbidity and mortality. Indirect implications are defined as the effect of the influence of emerging zoonotic disease on two groups of people, namely: health professionals and the general public. Professional assessment of the importance of these diseases influences public health practices and structures, the identification of themes for research and allocation of resources at both national and international levels. The perception of the general public regarding the risks involved considerably influences policy-making in the health field. Extensive outbreaks of zoonotic disease are not uncommon, especially as the disease is often not recognised as zoonotic at the outset and may spread undetected for some time. However, in many instances, the direct impact on health of these new, emerging or re-emerging zoonoses has been small compared to that of other infectious diseases affecting humans. To illustrate the tremendous indirect impact of emerging zoonotic diseases on public health policy and structures and on public perception of health risks, the authors provide a number of examples, including that of the Ebola virus, avian influenza, monkeypox and bovine spongiform encephalopathy. Recent epidemics of these diseases have served as a reminder of the existence of infectious diseases and of the capacity of these diseases to occur unexpectedly in new locations and animal species. The need for greater international co-operation, better local, regional and global networks for communicable disease surveillance and pandemic planning is also illustrated by these examples. These diseases have contributed to the definition of new paradigms, especially relating to food safety policies and more generally to the protection of public health. Finally, the examples described emphasise the importance of intersectorial collaboration for disease containment, and of independence of sectorial interests and transparency when managing certain health risks.

Animals↗
PubMed2000

Inhibition of apatite formation by vitronectin.

This study investigated the concentration-dependent effect of vitronectin (VN), a glycoprotein of the bone matrix, on apatite formation and growth. Precipitation trials in metastable solution and in a pH-controlled solution system showed an inhibition of apatite microcrystal formation by VN. In the presence of biphasic calcium-phosphate ceramic, transmission electron microscopy showed a reduction of precipitated microcrystal size: precipitates were significantly smaller than in ionic simulated body fluid without proteins or in the presence of type I collagen as a negative control. Moreover, the size of the precipitated microcrystals was reduced in a dose-dependent manner. Two indirect methods showed that calcium-phosphate precipitation was inhibited by VN. It would appear that VN prevents apatite formation by inhibiting the growth of apatite crystals rather than by secondary nucleation, as in the case of osteopontin, a bone-specific protein.

Apatites↗
PubMed2000

[In vitro effects of growth hormone on osteoclastic activity: clinical applications].

PURPOSE OF THE STUDY: This study was designed to investigate the in vitro effects of human growth hormone (hGH) on osteoclastic resorption in a nonfractionated rabbit bone cell model. MATERIAL AND METHODS: Rabbit bone cells were cultured on dentine slices in the presence of parathyroid hormone and vitamin D3. The percentage of dentine slice surface resorbed, number of lacunae per surface unit and mean area of lacunae were compared between cell cultures grown in the presence of graded concentrations of hGH and human insulin-like growth factor-1 (hIGF-1) and controls. RESULTS: After 4 days of culture, rabbit bone cells cultured on dentine slices in the presence of hGH and hIGF-1 showed significantly stimulated osteoclastic resorption activity. When neutralizing anti-hIGF-1 anti-serum (4 microg/l) was added to the starting culture, the stimulatory effects of hIGF-1 and hGH on osteoclastic resorption activity were totally abolished. DISCUSSION: These findings indicate that the effects of hGH stimulation on osteoclastic resorption in vitro are mediated via local hIGF-1 secretion by stromal cells such as osteoblasts. Proteases appear to play a role in the degradation of the organic matrix. Our experiments show that hIGF-1 and hGH stimulate the production of matrix metalloproteinases MMP-9 and MMP-2. Similar to the resorption activity, hGH stimulates protease activity via stromal cell production of hIGF-1. CONCLUSION: This study suggests that natural or synthetic MMP inhibitor modulation of protease activity could reduce the degradation of the organic matrix and then prevent, for example, inflammatory reactions subsequent to prosthetic loosening.

Animals↗
PubMed1999

Osteogenic potential in vitro of human bone marrow cells cultured on macroporous biphasic calcium phosphate ceramic.

Calcium phosphate ceramics are synthetic bone substitutes that promote bone formation by osteoconduction. However, they have shown an osteogenic potential in vivo in animal models when associated with bone marrow cells. In order to develop an osteogenic human "hybrid material," we studied the in vitro osteogenic potential of human bone marrow cells cultured on macroporous biphasic calcium phosphate (BCP) pellets in the presence of dexamethasone with or without 1alpha,25 dihydroxyvitamin D3. We were examining, in particular, their mesenchymal stem cell proliferation and hematopoietic potential. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and immunological characterization of the extracellular matrix formed by these cells. The specimens were observed by scanning and transmission electron microscopy. Human mesenchymal stem cells proliferated on macroporous BCP ceramic, with a doubling time delayed at the beginning of the culture as compared to the cultures realized on plastic. These cells maintained a hematopoietic activity identical to that of cultures performed in plastic wells. The proliferating mesenchymal stem cells expressed an osteoblastic phenotype, as shown by alkaline phosphatase activity and the synthesis in ceramic macropores of an extracellular matrix composed of fibronectin, osteocalcin, and collagen I (but not collagen III). In addition, numerous microcrystals of apatite precipitated on the extracellular matrix, producing a mineralized fibrillar network within the ceramic not observed with cell cultures realized on plastic. These results demonstrate that human mesenchymal stem cells cultured on macroporous BCP ceramic express and conserve their osteoblastic phenotype even after one month of culture and that these osteogenic cells are able to form new bone matrix in a BCP ceramic in vitro.

Biocompatible Materials↗
PubMed1999

Influence of biphasic calcium phosphate granulometry on bone ingrowth, ceramic resorption, and inflammatory reactions: preliminary in vitro and in vivo study.

Calcium-phosphate ceramics used in surgery, as bone-bonding materials, are currently available in different forms (blocks, granules, etc.). However, progress in noninvasive surgery has favored the development of injectable composite materials associating a polymeric and a dusty mineral phase. The purpose of this study was the in vivo evaluation of biphasic calcium phosphate of various grains sizes, to elucidate the role of granulometries in ceramic degradation/resorption, bone ingrowth, and inflammatory reactions. Three particle sizes were compared: 10-20, 80-100, and 200-400 microm. The 10-20-microm powders provided the best bone ingrowth, with a higher resorption/degradation rate in conjunction with stronger early inflammatory reactions. The 200-400-microm powders showed higher bone ingrowth than 80-100-microm ones, indicating that properties of cell recruitment for osseous apposition and mechanical support for bone bonding may both play a role in both ingrowth mechanisms. Our results suggest that the strong inflammatory reaction in 10-20-microm granulated powders was due to a faster reversal of the resorption/apposition sequence in bone. This may have resulted from massive release of bone ingrowth factors, which implies that the brief inflammatory process observed in the early stages of implantation was favorable to the osteoconduction process.

Bone Development↗
PubMed1999

Biological activities of sustained polymyxin B release from calcium phosphate biomaterial prepared by dynamic compaction: an in vitro study.

Calcium phosphate ceramics (CaP) have recently been proposed as a potential matrix for a bioactive drug delivery system (DDS) in which the effect in situ of a released therapeutic agent is favored by the biocompatibility, osteoconductivity, and bioresorption of the ceramic material. Polymyxin B (PMB) is a polypeptidic antibiotic which undergoes thermodamage above 60 degrees C. The dynamic compaction method was developed to consolidate the drug load on CaP powder without external heating. Two projectile velocities (50 and 25 m/s) were used here to achieve powder consolidation. Among the different techniques used to associate therapeutic agents with CaP, wet adsorption was performed before the dynamic compaction process. The PMB release profile was measured by a capillary electrophoresis technique, CaP crystallography was studied by x-ray diffraction, and CaP physicochemical analysis was performed by infrared spectroscopy. The biological activities of PMB-loaded compacted CaP were determined by the effect of the antibiotic and monocyte/macrophage degradation on compact surfaces. PMB release began after 2-3 days of incubation for blocks compacted at 25 m/s velocity and on day 5 for those compacted at 50 m/s velocity. A discrepancy was noted between the amounts of PMB released (0.5-2.1 mg) and the amounts initially compacted (2-8 mg) with CaP powder. The biological activities (antibacterial activity and inhibited lipopolysaccharide effects on monocyte/macrophage CaP degradation) of PMB released from compacted calcium-deficient apatite were unaltered. Thus, dynamic compaction allows PMB to be used with CaP ceramics without any loss in its integrity and biological effects.

Anti-Bacterial Agents↗
PubMed1999

Expression of leukemia inhibitory factor by cartilage-forming tumors of bone: an immunohistochemical study.

Recent studies have implicated leukemia inhibitory factor in connective-tissue metabolism involving the remodeling of bone and the destruction of cartilage tissue. This cytokine, which has also been implicated in the proliferation of solid tumor, is expressed by osteotropic tumor cell lines. The present study investigated the presence of leukemia inhibitory factor in cartilage tissue harvested from cartilage-forming bone tumors. Immunohistochemical study showed that it was present in all benign enchondromas (n = 8) and malignant chondrosarcomas (n = 6) but not in control tissue (n = 3). The cytokine was localized in only cytoplasmic areas of cartilage cells. The number of stained cells ranged from less than 5% in enchondroma of the hand to more than 70% in grade-III chondrosarcoma. Moreover, high levels of leukemia inhibitory factor were found in the primary culture of tumor tissues (n = 7). These results question the significance of leukemia inhibitory factor in tumor-associated bone resorption and the potential role of this cytokine as a prognostic marker.

Adolescent↗
PubMed1999

Presence of leukaemia inhibitory factor (LIF) and LIF-receptor chain (gp190) in osteoclast-like cells cultured from human giant cell tumour of bone. Ultrastructural distribution.

The behaviour of multinucleated giant cells (MNC) obtained from a giant cell tumour of the tibia and cultured on glass coverslips or on devitalized dentin slices was investigated using light and electron microscopy. Cells were studied in the presence or absence of LIF a cytokine known to be involved in bone turnover and to act as a growth factor in some solid tumours. The direct effect of LIF on MNC was examined by a post-embedding colloidal gold immunocytochemistry process using human anti-LIF and anti-LIF-receptor (chain gp190) antibodies. After 7 days of culture, the MNC obtained displayed osteoclast immunocytochemical features. Moreover, these MNC were able to resorb large amounts of dentin and presented typical features of active osteoclasts. Immunolocalization of LIF and LIF-receptor revealed the presence of this cytokine and its receptor within the cytoplasm and nucleus of active resorbing MNC. LIF upmodulated MNC number and nucleation but decreased their ability to resorb dentin. The present study suggests that MNC obtained from human GCT, currently considered as osteoclast-like cells, are targets for LIF and may be a source of LIF production in this pathological condition.

Bone Neoplasms↗