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At least 1,207 records · Page 67Linked to original sources
PubMed2006

Effect of compressive force on the expression of MMPs, PAs, and their inhibitors in osteoblastic Saos-2 cells.

Bone matrix turnover is regulated by matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), and the plasminogen activation system, including tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1). We previously demonstrated that 1.0g/cm(2) of compressive force was an optimal condition for inducing bone formation by osteoblastic Saos-2 cells. Here, we examined the effect of mechanical stress on the expression of MMPs, TIMPs, tPA, uPA, and PAI-1 in Saos-2 cells. The cells were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum and with or without continuously compressive force (0.5-3.0g/cm(2)) for up to 24h. The levels of MMPs, TIMPs, uPA, tPA, and PAI-1 gene expression were estimated by determining the mRNA levels using real-time PCR, and the protein levels were determined using ELISA. The expression levels of MMP-1, MMP-2, MMP-14, and TIMP-1 markedly exceeded the control levels at 1.0g/cm(2) of compressive force, whereas the expression levels of MMP-3, MMP-13, TIMP-2, TIMP-3, TIMP-4, tPA, uPA, and PAI-1 markedly exceeded the control levels at 3.0g/cm(2). These results suggest that mechanical stress stimulates bone matrix turnover by increasing these proteinases and inhibitors, and that the mechanism for the proteolytic degradation of bone matrix proteins differs with the strength of the mechanical stress.

Cell Line, Tumor↗
PubMed1997

Expression of matrix metalloproteinase-9 mRNA in osteoporotic bone tissues.

Matrix metalloproteinases (MMPs), a sort of important enzymes involved in extracellular matrix metabolism, play critical roles in the process of tissues remodeling, wound healing and metastasis of tumors. Dot blot and in situ hybridization were used in this study to detect the expression and localization of MMP-9, an important proteolytic enzyme implicated in bone resorption in bone tissues. The results showed that the level of MMP-9 mRNA expression in osteoporotic bone tissues was significantly higher than that in normal control group and the cell types that expressed MMP-9 mRNA included mono- and multi-nuclear osteoclasts and some lining cells on the surface of bone matrix. It was suggested that MMP-9 play a key role in the development of bone loss in osteoporosis.

Animals↗
PubMed1982

Experimental surface or volume deposition of radionuclides in post-mortem specimens of trabecular bone.

Techniques are described that have been developed to contaminate post-mortem specimens of human trabecular bone uniformly and artificially with three different radionuclides, 14C, 45Ca and 32P, so as to produce either a uniform volume deposition of radionuclide through the bone matrix or an 'infinitely' thin layer of radionuclide on the trabecular surfaces. Uniform volume depositions of 45C and 32P were produced by neutron activation and the 14C volume distribution was successfully achieved by rehydrating the bone matrix with 14C-labelled urea solution. Surface depositions of isotope were attempted by introducing a radionuclide into solution. Surface depositions of isotope were attempted by introducing a radionuclide into solution which was in equilibrium with trabecular bone and depositions approximating to an 'infinitely' thin layer of isotope were achieved for 32P and 14C using adenosine triphosphate-labelled molecules. Ionic calcium penetrates the bone matrix very rapidly and the best 45Ca surface deposition that could be produced penetrated the trabecular surface to an average depth of about 10 micrometer. The uniformity of deposition was analysed by autoradiography and the thickness of the 'surface' layer of radionuclide was estimated using microdensitometer scans across selected strands of the autoradiograph and comparing the film density profiles thus produced with calculations.

Bone and Bones↗
PubMed1999

An osteoconductive collagen/hyaluronate matrix for bone regeneration.

A new type of collagen-hyaluronate (COL/HA) matrix was synthesized by cross-linking collagen fibers with modified hyaluronate polymers bearing active formyl groups. The resulting matrix is a three-dimensional scaffold consisting of interconnected pores with an average size of 40 microm and a high pore volume/surface area ratio. The covalent nature of the bond between the collagen fibers and the modified hyaluronate was demonstrated by extended elution with phosphate buffered saline and by extraction in increasing ionic gradients. The fraction of covalently bound hyaluronate in the matrix ranged from 5 to 25 w%. The total hyaluronate content of the COL/HA matrix affected both the in vitro non-enzymatic and enzymatic degradation as well as the in vivo turnover. When implanted in cranial defects in rats, the COL/HA matrix demonstrated good biocompatibility and exhibited greater osteoconductive potential than matrices composed of either cross-linked collagen or cross-linked hyaluronate alone.

Animals↗
PubMed1993

Osteoinductive, morphologic, and biomechanical properties of autolyzed, antigen-extracted, allogeneic human bone.

Autolyzed, antigen-extracted, allogeneic (AAA) bone was prepared from human cortical bone and its morphologic, biomechanical, and osteoinductive properties were compared with untreated (frozen) as well as lyophilized human bone. Scanning electron microscopy revealed removal of inorganic calcium phosphates and persistence of shrunken collagen fibrils on the surface of AAA bone matrix. Biomechanical testing of differently prepared bone samples showed that lyophilization increased both the modulus of elasticity (P < .00001) and the compressive strength (P < .00001). Depending on the depth of decalcification in the preparation of AAA bone, both measured values decreased in rehydrated AAA bone compared with untreated bone (P < .00001). Completely demineralized and rehydrated AAA bone was soft, flexible, and showed very little compressive strength. Differences in biomechanical behavior between samples drilled longitudinally or perpendicularly to the diaphyseal bone axis were observed. Xenogeneic human bone samples were implanted in muscle pouches of Sprague-Dawley rats for 6 weeks. AAA bone implants showed chondrogenesis and osteogenesis in 50% of the cases, while untreated or lyophilized bone implants induced no new cartilage or bone formation. As decalcification exposed xenogeneic organic matrix components, AAA bone implants provoked the highest inflammatory reaction. When AAA bone samples were implanted in immunosuppressed rats, the inflammatory reaction was suppressed and 94% of the implants showed endochondral bone formation. The chondroinductivity of the bone samples also was tested in vitro using neonatal rat muscle tissue to avoid interference with inflammatory cells and secreted cytokines. In this assay, 68% of AAA bone samples induced chondroneogenesis, while untreated as well as lyophilized bone samples failed to induce any cartilage formation. The results clearly demonstrate that AAA bone has osteoinductive properties. Biomechanical stability of AAA bone implants depends on the degree of demineralization. Thus, they can be prepared in an appropriate manner for different indications in oral and maxillofacial surgery.

Animals↗
PubMed1989

Bone induction in a composite allogeneic bone/alloplastic implant.

This study evaluated the morphogenetic properties of the bone matrix as a biological delivery system in a composite allogeneic bone/alloplastic implant placed in extraskeletal recipient sites in rats. Seventy-two allogeneic diaphyseal bone cylinders were chemosterilized to obtain autolyzed antigen-extracted allogeneic (AAA) bone and implanted in twenty 140- to 160-day-old rats. In 30 implants, porous hydroxyapatite biomatrix (HAB) was inserted into the AAA bone cylinders creating the composite implants. Serial sections from the specimens harvested at 23, 30, 45, 53, and 63 days showed that 84% of the AAA bone cylinders induced the differentiation of variable amounts of endochondral bone and that in 61% bone formed in the interior of the cylinders; 74% of the composite implants had no bone-inductive effect, recruiting instead macrophages and multinucleated giant cells at the HAB/mesenchymal interface. In all instances bone failed to form within the porous HAB or in proximity to the AAA bone matrix facing the interior of the cylinders. When present, bone formed only in localized areas within the matrix. Histologic analysis showed that high deposits of induced bone are correlated to high levels of matrix vascular invasion and mesenchymal cell aggregation. Within the limits of this study on rodents, the results suggest that the HAB inhibits and delays the local differentiation of induced bone in the composite implants.

Animals↗
PubMed1995

The effects of cytokines and growth factors on osteoblastic cells.

In this short review, some regulatory mechanisms that are involved in the control of normal bone formation are proposed, based on several in vivo and in vitro models our group has utilized recently to study osteoblast differentiation and mineralized bone matrix formation. Of course, these proposals must be assessed in the light of the limitations of the models, which probably represent a simplification of the complex and different ways in which normal mammalian bone is formed at different sites. Nevertheless, it is likely that the same general types of control mechanisms are active in each of the different types of bone formation. In adult humans, bone formation predominantly occurs by remodeling, the process by which bone which has recently been resorbed by osteoclasts is replaced by teams of osteoblasts. Other types of bone formation such as endochondral bone formation and appositional bone formation are also important, particularly during growth and adolescence. The end results of each of these processes are the same, namely a complex mineralized proteinaceous bone matrix. These processes are modulated by systemic hormonal influences, which are particularly important with respect to pituitary hormones and sex steroids during growth and adolescence, and by local cellular microenvironmental differences. The former will not be discussed here. Rather, we will concentrate on the local events and factors which are likely involved in the bone formation process occurring during normal bone remodeling.

Adult↗
PubMed2004

Carrier dependent cell differentiation of bone morphogenetic protein-2 induced osteogenesis and chondrogenesis during the early implantation stage in rats.

To evaluate the osteoinductive effects of recombinant human bone morphogenetic protein (rhBMP)-2 during the early stages of rat ectopic bone formation, we prepared two distinct carriers. Two carriers, insoluble bone matrix (IBM) and fibrous glass membrane (FGM) were combined with rhBMP-2 and implanted into the backs of rats to evaluate the osteoinductive effects of the two rhBMP-2 carrier systems. Insoluble bone matrix particle size was 320 to 620 microm. Fibrous glass membrane was constructed from unwoven glass fibers 1 microm in diameter. Alkaline phosphatase (ALP) activity and type II collagen were detected in IBM/rhBMP-2 at 5 days postimplantation. Calcium (Ca) was also detected in IBM/rhBMP-2 at 7 and 9 days postimplantation. In contrast, ALP and type II collagen were detected in FGM/rhBMP-2 at 7 days. Calcium was undetected, indicating that the bone formation in IBM/rhBMP-2 proceeded faster than in FGM/rhBMP-2 during the early stage of BMP-induced osteogenesis. In addition, mRNA expression level of KDR, a receptor for vascular endothelial growth factor, was also increased in IBM/rhBMP-2. To investigate the in vivo release profile of rhBMP-2, iodine 125 ((125)I)-labeled BMP-2-incorporating IBM and FGM implants were inserted into the back subcutis of mice. More than 60% of the rhBMP-2 was released from the IBM/rhBMP-2 carrier within 1 day after implantation, whereas 50% of the rhBMP-2 was released from the FGM/rhBMP-2 10 days postimplantation. These results indicated that osteo- and chondrogenesis depends highly upon the geometry of the carrier and the in situ retention of rhBMP-2 during the early stage of rhBMP-2 induced bone formation.

Alkaline Phosphatase↗
PubMed1996

Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3-E1 cells.

Bone formation involves several tightly regulated gene expression patterns of bone-related proteins. To determine the expression patterns of bone-related proteins during the MC3T3-E1 osteoblast-like cell differentiation, we used Northern blotting, enzymatic assay, and histochemistry. We found that the expression patterns of bone-related proteins were regulated in a temporal manner during the successive developmental stages including proliferation (days 4-10), bone matrix formation/maturation (days 10-16), and mineralization stages (days 16-30). During the proliferation period (days 4-10), the expression of cell-cycle related genes such as histone H3 and H4, and ribosomal protein S6 was high. During the bone matrix formation/maturation period (days 10-16), type I collagen expression and biosynthesis, fibronectin, TGF-beta 1 and osteonectin expressions were high and maximal around day 16. During this maturation period, we found that the expression patterns of bone matrix proteins were two types: one is the expression pattern of type I collagen and TGF-beta 1, which was higher in the maturation period than that in both the proliferation and mineralization periods. The other is the expression pattern of fibronectin and osteonectin, which was higher in the maturation and mineralization periods than in the proliferation period. Alkaline phosphatase activity was high during the early matrix formation/maturation period (day 10) and was followed by a decrease to a level still significantly above the baseline level seen at day 4. During the mineralization period (days 16-30), the number of nodules and the expression of osteocalcin were high. Osteocalcin gene expression was increased up to 28 days. Our results show that the expression patterns of bone-related proteins are temporally regulated during the MC3T3-E1 cell differentiation and their regulations are unique compared with other systems. Thus, this cell line provides a useful in vitro system to study the developmental regulation of bone-related proteins in relation to the different stages during the osteoblast differentiation.

Alkaline Phosphatase↗
PubMed2005

BMP binding peptide: a BMP-2 enhancing factor deduced from the sequence of native bovine bone morphogenetic protein/non-collagenous protein.

Forty years ago, Marshall Urist described a partially purified extract of demineralized bone matrix which induced the formation of ectopic bone. This substance, bone morphogenetic protein/non-collagenous protein (BMP/NCP), was never purified to homogeneity but other investigators used similar starting materials to clone a number of recombinant BMPs. Urist recognized that his material probably contained the BMPs which had been cloned by others but always contended that it contained another, more potent, bone inducing material which differed significantly in its physical and chemical properties from the known BMPs. We have used Urist's protocol to isolate a protein that has the chemical and physical properties of Urist's "BMP". It is an 18.5 kD fragment of the bone matrix protein, SPP-24. This fragment contains the cystatin-like domain of SPP-24. We have located a 19 amino acid region which is similar to the TGF-beta/BMP-binding region of fetuin, a member of the cystatin family of protease inhibitors. A cyclic peptide, which we call BMP binding peptide (BBP) was generated using this sequence. The peptide avidly bound rhBMP-2 with a KD of 3 x 10(-5) M. When implanted alone in mouse muscle, the peptide frequently induced dystrophic calcification. When implanted with rhBMP-2, the peptide enhanced the osteogenic activity of the recombinant molecule. We hypothesize that Urist's "BMP" was a fragment of SPP-24 which influenced bone induction by binding to bone morphogenetic proteins. BBP may be clinically useful because of its effects on other bone-inducing substances.

Amino Acid Sequence↗
PubMed2000

Bone growth on and resorption of calcium phosphate coatings obtained by pulsed laser deposition.

Three different calcium phosphate coatings of crystalline hydroxyapatite (HA), alpha- and beta-tricalcium phosphate (alpha+beta-TCP), or amorphous calcium phosphate (ACP) obtained by pulsed laser deposition on Ti-6Al-4V were incubated in a potentially osteogenic primary cell culture (rat bone marrow) in order to evaluate the amount and mode of mineralized bone matrix formation after 2 weeks with special emphasis on the type of interfacial structure that was created. Evaluation techniques included fluorescence labeling and scanning electron microscopy. The resistance to cellular resorption by osteoclasts was also studied. Bone matrix delaminated from the ACP coatings, while it remained on the HA and the alpha+beta-TCP coatings even after fracturing. A cementlike line was seen as the immediate contiguous interface with the nondegrading dense HA surface and with the surface of the remaining porous beta-TCP coating. Highly dense and crystalline HA coatings do not dissolve but are capable of establishing a strong bond with the bone matrix grown on top. Chemical and mechanical bonding were considered in this case. Cellular resorption was practically not observed on the HA coatings, but it was observed on the alpha+beta-TCP coatings. Resorption took place as dissolution that was due to the acidic microenvironment.

Alloys↗
PubMed1989

Immunocytochemical localization of BGP in human bones in various developmental stages and pathological conditions.

Bone gamma-carboxyglutamic acid containing protein (BGP) was isolated from human bone and anti-BGP antibody was produced in rabbits. Localization of BGP was investigated immunocytochemically by light and electron microscopy in human bones in various developmental stages and pathological conditions. In the bones of a 12 week fetus, osteoblasts stained strongly in areas of bone formation. However in bones of late fetal stages and in newborns and adults, BGP was localized predominantly in the osteoid and bone matrix in the ossifying front. Osteoblasts and osteocytes also stained positive, but less dominantly than in the early fetus. Electron microscopy showed that BGP was localized in the ER and Golgi cisternae of osteoblasts and osteocytes, and the collagen fibers of the osteoid and bone matrix. The intensity and distribution of staining were not significantly different in osteoporosis and osteoarthritis. These observations indicate that BGP is synthesized by osteoblasts most actively in early fetal life and is then deposited on collagen fibers of the osteoid and bone matrix.

1-Carboxyglutamic Acid↗
PubMed1999

[Physiopathology of tumor-induced osteolysis].

Osteolysis, the most common expression of bone tumor, can cause pain, pathological fracture, epidural spinal cord compression and hypercalcemia. Multinucleated osteoclast-like cells, the main agents in bone resorption, are numerous in benign giant cell tumor of bone and can be recruited and activated by various carcinoma cell lines in vitro in animal models. Polykarion macrophages are also able to resorb bone matrix in a favourable tumoral environment. Direct bone resorption by tumor cells has recently been described in vitro and in vivo in animals. The presence of diffusible substances such as hormones, cytokines and growth factors creates a favourable microenvironment for stimulation of osteoclast-like cells and polykarion macrophages functional ability to resorb bone matrix. These mediators act within a complex but still unelucidated network involving high cell production (tumor cells, normal and reactional stroma as well as hematopoietic cells) and many targets (tumor production (tumor cells, normal and reactional stroma as well as hematopoietic cells) and many targets (tumor cells, monocyte/macrophage lineage cells, and osteoclast-like cells). The presence in the same environment of all these stimulating factors for tumor cell growth and resorbing ability could explain the vicious circle of tumoral and osteolytic progression. A better understanding of the complex mechanism of tumor induced osteolysis is essential for improving the conventional surgical approach to this pathology.

Animals↗
PubMed1996

[An experimental study on the relationship between BMP's activity and its carrier].

To find out the relationship between human bone morphogenetic protein's activity and its carrier and to document the clinical application of BMP, we investigated six kinds of BMP carrier's influence upon hBMP's osteogenic activity with small sample size at first. Then three kinds of carriers selected from the six, added with the seventh carrier, were investigated with large sample size. The result showed that the compound of hBMP and hDDBM had best osteogenic ability. The human bone matrix had been formerly demineralized and extracted without hBMP. The hDDBM showed porous structure under SEM, its mean pore's diameter was 127 +/- 34 microns. It was demonstrated that the function of demineralized bone matrix extracted without BMP (i.e. DDBM) was related not only to its pore's diameter, but to the fibrolike matter in it as well. With the method of BMP bioassay, BMP was composited with carrier, then the compound was injected into the calf of mouse. This made BMP's bioassay become simple and reliable.

Animals↗
PubMed1999

Disaggregated osteoclasts increase in resorption activity in response to roughness of bone surface.

The roughness of the bone matrix surface affects osteoblastic differentiation. However, the effect of the roughness of the matrix surface on osteoclastic bone resorption remains to be studied. We examined the latter effect using disaggregated osteoclasts from neonatal rats. The resorption pit number and the total pit area on the rough surface were not different from those on smooth surfaces after 1 day, but they were 2 or more times higher after 3 days. The number of osteoclasts was not different on bone slices with either smooth or rough surfaces at 3 days. The alkaline phosphatase (ALP)-positive osteoblasts were relatively rare in both types of slices at first, then the number and the diameter of the enzyme-positive cells and the clusters preferentially increased on the rough bone slices. When hydroxyurea was added to the culture in order to suppress the proliferation and the subsequent differentiation of osteoblastic cells on rough surfaces, the increase in resorption on the rough surfaces was effaced; however, this agent had little affect on resorption of the smooth surfaces. The addition of ALP-positive cells to disaggregated osteoclasts increased bone resorption on the smooth surface. The results suggest that osteoblast development and subsequently bone resorption by osteoclasts is enhanced by the roughness of matrix surfaces.

Alkaline Phosphatase↗
PubMedDate not supplied

Bisphosphonate conjugation to proteins as a means to impart bone affinity.

Growth factors are endogenous proteins capable of stimulating new bone formation, but their clinical benefit for systemic stimulation of bone mass has not been demonstrated. The critical challenge is to deliver a significant dose of the proteins to bone after intravenous injection. This challenge may be overcome by derivatizing proteins with ligands that exhibit a high bone affinity (e.g., bisphosphonates). To demonstrate the feasibility of this approach, 1-amino-1,1-diphosphonate methane (aminoBP) was conjugated to a model protein, albumin. The conjugation was performed by (1) converting the amino group of aminoBP to a thiol group using 2-iminothiolane, (2) derivatizing the albumin amino groups with a thiol-reactive sulfosuccinimidyl-4-(N-maleimidomethyl)-1-cyclohexane carboxylate, and (3) reacting the derivatized albumin with thiolated aminoBP. Typically, 1-4 aminoBP molecules per albumin were obtained. The conjugated albumin exhibited a high affinity to hydroxyapatite that was proportional to the extent of conjugation. The conjugates were shown to exhibit a high affinity to bone matrix in vitro in a serum-containing medium. Once bound to bone matrix, the conjugates were found to desorb more slowly than the unmodified albumin, especially from bone whose organic matrix was removed by ashing. In conclusion, conjugation of bisphosphonates to albumin was shown to impart a high bone affinity to the protein, and such conjugates can be potentially targeted to bone.

Animals↗
PubMed1977

Osteoid: an ultrastructural study.

Iliac crest bone biopsy specimens from 34 patients were examined with the electron microscope. Although the biopsy examinations were undertaken because of suspected metabolic or hematopoietic disease, neither clinically nor by light microscope was any evidence of disease identified. The layer of bone matrix between the osteoblast and the mineralized bone, usually referred to as "osteoid," is found not to be a homogeneous mass but to show a constant sequence of maturation and organization of collagen fibrils and mucopolysaccharides. This pattern was found to be modified in a situation of rapid bone formation such as normal fetal bone or in disease states such as Paget's disease of bone. These observations are of paramount importance in the evaluation of metabolic diseases of bone and in the identification of bone formation by mesenchymal neoplasms.

Biopsy↗
PubMed2001

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog.

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4% pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in one of the four alpha-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.

Animals↗