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Biomedical subjects

M C Meikle

Publications and source records attributed to M C Meikle.

At least 73 records · Page 4Linked to original sources
PubMed1985

Pig interleukin 1 (catabolin) is a potent stimulator of bone resorption in vitro.

A homogeneous form of pig interleukin 1 (catabolin) stimulates the resorption of mouse bones in culture. Concentrations as low as 25 pM are effective, demonstrating that it is more potent than 1,25-dihydroxy-vitamin D3 in our assay system. Catabolin was originally defined by its ability to stimulate glycosaminoglycan release from cartilage in culture and purified from pig mononuclear leucocyte supernatants. It also augments lectin-induced thymocyte proliferation, indicating that it is a form of pig interleukin 1. Bone resorbing factors are synthesized by other cell types, including fibroblasts and osteoblasts; we suggest that such cytokines are important in mediating the action of systemic hormones on bone.

Animals↗
PubMed1984

Mouse osteoblasts synthesize collagenase in response to bone resorbing agents.

Bone cells isolated from mouse calvariae by a sequential digestion procedure have many osteoblast characteristics: they respond to PTH and prostaglandin E2 by activation of adenylate cyclase but not to calcitonin, they stain for alkaline phosphatase and they make only type I collagen. In confluent monolayer culture, they do not secrete collagenase in appreciable quantities, unless stimulated with resorptive substances such as PTH, prostaglandin E2, 1,25(OH)2 vitamin D-3 and monocyte-conditioned medium. This suggests they play a direct role in bone resorption.

Adenylyl Cyclases↗
PubMed1984

A factor synthesized by rabbit periosteal fibroblasts stimulates bone resorption and collagenase production by connective tissue cells in vitro.

Unstimulated monolayer cultures of confluent rabbit periosteal fibroblasts synthesize a factor that stimulates bone resorption in vitro. Furthermore it stimulates rabbit chondrocytes and mouse osteoblasts to synthesize collagenase. The factor has no effect on dead bone in culture, and its activity on live bone is mediated principally by osteoclasts, since it is 75% inhibited by salmon calcitonin. Characterization of the factor by gel filtration and isoelectric focusing indicates an Mr in the range 15000-25000 and a pI corresponding to approx. pH 4.7. These biological and physiochemical properties are similar to those reported for a factor released by peripheral blood monocytes. However, whereas human monocyte factor in both the crude and partially-purified state exhibits interleukin-1 activity, crude and fractionated periosteal fibroblast-conditioned medium does not. This is the first report of a conditioned medium containing a molecule like the monocyte-factor which appears to have no interleukin 1 activity. The factor may be synthesized by a wide range of cell types, and could have an important role in mediating connective tissue degradation during both physiological and pathological resorption.

Animals↗
PubMed1984

The use of in vitro models for investigating the response of fibrous joints to tensile mechanical stress.

To clarify the role of mechanical deformation in the remodeling of fibrous joints, organ culture systems have been developed to apply mechanical stress to cranial sutures under controlled experimental conditions. Tensile mechanical stress applied to cranial sutures from newborn rabbits produces a two- to threefold increase in protein synthesis and a twofold increase in collagen synthesis that can be detected within 6 hours. There is also a threefold increase in the DNA content of the sutures after 48 hours. Under normal conditions sutural fibroblasts synthesize type I collagen but respond to tensile deformation by synthesizing significant amounts of type III collagen. This suggests that the biomechanical environment of a connective tissue cell is an important determinant of the collagen type synthesized. However, the effect is likely to be an indirect one by virtue of its influence on the metabolic activity of the cells. Mechanically activated cells do not preferentially synthesize structural proteins, since mechanical stress stimulates the synthesis not only of structural macromolecules but also of the enzymes responsible for their specific hydrolysis. This is not accompanied by increased degradation, however, perhaps because the metalloproteinase inhibitor TIMP synthesized by the tissues is also increased. Confluent rabbit and mouse periosteal fibroblasts synthesize and release into the culture medium factors that can inhibit bone cell proliferation and stimulate bone resorption in vitro. It seems likely that further investigation of the interaction between fibroblasts and osteoblasts at the bone--fibrous tissue interface will require a reassessment of current thinking concerning the mechanisms regulating sutural osteogenesis.

Animals↗
PubMed1983

Stimulation of bone resorption in vitro by a non-prostanoid factor released by human monocytes in culture.

Cultured human monocytes produce a non-prostanoid factor which stimulates bone resorption in vitro. Production of the factor is not dependent on prostaglandin synthesis, but stimulation of resorption by the factor does involve prostaglandin production by bone. Salmon calcitonin inhibits the stimulatory activity by up to 80%. Production of the factor is not increased by the presence of lymphocytes in the monocyte cultures. Partial purification of the bone-resorbing activity by Ultrogel ACA 54 chromatography shows that it has an apparent molecular weight between 12 000 and 20 000. We suggest that the resorptive activity is due to an interleukin 1-like factor rather than an osteoclast activating factor.

Animals↗
PubMed1982

Anterior mandibular displacement and condylar growth. An experimental study in the rat.

Anterior displacement of the mandible was produced in twenty-eight 1-month-old female rats by two methods: (1) cast-gold splints cemented to the maxillary incisor teeth and (2) a removable stainless steel mesh appliance worn 6 hours each day, during which time the animals were sedated. The controls were littermates without appliances and in the mesh group were also sedated. Animals in the splint group were killed after 24 hours, 1 week, and 1 month; those in the mesh group were killed after 24 hours and after 1 week. the condyles were removed and cultured for 24 hours in medium containing 3H-thymidine. One condyle from each animal was processed for routine histologic and autoradiographic study. The other was digested in phosphate-buffered saline containing RNA-ase and pronase, and the specific activity of 3H-thymidine incorporation expressed as dpm/microgramDNA. Anterior mandibular displacement produced by both methods failed to result in a significant increase in the incorporation of 3H-thymidine into explant DNA. In the 7-day mesh experiment, however, there was a significant increase in the DNA content of the condylar explants from the displacement group, suggesting an increase in the cell population. This finding should be treated with caution because of the small numbers of animals involved, but it indicates an important area for further study. Changes in the distribution of labeled cells within the proliferative zone (PZ) were also observed autoradiographically in the mesh group, but there was little to suggest that mandibular displacement was accompanied by a significant increase in cell division within the PZ. Remodeling changes affecting both the articular tissue and the subchondral bone were a characteristic feature of the 1-month bit plane group.

Animals↗
PubMed1982

Rabbit cranial suture fibroblasts under tension express a different collagen phenotype.

We present evidence that cells in fibrous joints respond to tensile mechanical stress by synthesizing significant quantities of type III collagen. Under normal conditions sutural fibroblasts synthesize type I collagen. Type III comprised some 20 per cent of the newly synthesized collagen in stressed joints, a level that was achieved within 24 h of the onset of tension and remained unchanged throughout a 4-day experimental period. These findings suggest that the biomechanical environment of a connective tissue cell is an important determinant of the type of collagen synthesized. However, we propose that the effect is likely to be an indirect one by virtue of its influence on the metabolic activity of the cells.

Animals↗
PubMed1982

Effect of streptococcal cell wall components on bone metabolism in vitro.

Cell was components from Streptococcus mutans NCTC 10449 and Streptococcus sanguis ATCC 10558 stimulated the release of 45Ca from prelabeled mouse calvariae in organ culture. Bone resorbing activity was not blocked by fetal calf serum. It was, however, blocked by calcitonin, an inhibitor of osteoclast-mediated bone resorption. Indomethacin, a prostaglandin synthetase inhibitor, partially blocked endogenous but not antigen-stimulated 45Ca, suggesting that antigen-stimulated bone resorption was not mediated by prostaglandins. The antigen preparations also had an inhibitory effect on the incorporation of 3H-proline and 3H-thymidine into explants of rabbit and rat calvariae, respectively. The inhibitory effect of antigen on 3H-proline incorporation was not altered by the presence of calcitonin, which suggests that it represented a real inhibition of protein synthesis and not a reflection that the bones were resorbing. These findings indicate that plaque bacterial antigens may contribute directly to the progressive loss of alveolar bone during periodontal disease. The assumption that only Gram-negative organisms play an important role In the etiology of periodontal disease appears incorrect.

Animals↗
PubMed1980

Effect of tensile mechanical stress on the synthesis of metalloproteinases by rabbit coronal sutures in vitro.

The application of a continuous tensile mechanical stress (30 g) to explants of coronal sutures from newborn rabbits (1-2 days) produced increases in enzyme activity of 33.7% for collagenase, 95.2% for gelatinase, and 35.9% for NMP III over a 4-day culture period. All three activities were in latent form and required activation with either 4-APMA or trypsin. The increases in enzyme activities were not accompanied by an alteration in the degradation of structural proteins. This was due to the ability of the cells to synthesize an inhibitor (mol wt 29,000 daltons) which complexed the increased quantities of enzyme. This necessitated a substantial stimulation of inhibitor production because there was still a residue of free inhibitory activity in the media of stressed cultures after 4 days. We previously showed using the same model system that coronal sutures respond to tensile mechanical stress by a two-fold increase in collagen synthesis. The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels.

Animals↗
PubMed1980

The dentomaxillary complex and overjet correction in Class II, division 1 malocclusion: objectives of skeletal and alveolar remodeling.

In recent years it has become apparent that there are limitations to the amount of tooth movement that can be accomplished by alveolar remodeling. Retraction of the maxillary incisor teeth should therefore be avoided during overjet correction if penetration of the palatal alveolar cortex is a probability. Since the Class II, Division 1 phenotype is characterized by abnormalities in both dentoalveolar process and maxillomandibular reactions, trying to compensate for the skeletal discrepancy through alveolar remodeling alone does not have logic on its side. Indeed, treatment philosophies based entirely on a concept of alveolar remodeling cannot be justified on biologic grounds. The most reliable method of avoiding destruction of the palatal alveolar cortex during overjet correction is by means of headgear mechanics designed to produce clinically significant skeletal remodeling. This holds as a general principle, even where extractions are an essential part of the treatment program. Furthermore, because the facial skeleton responds to mechanical deformation more readily in the growing person, the policy adopted by many orthodontists of deferring treatment until the permanent teeth have erupted has little to recommend it.

Alveolar Process↗
PubMed1979

Rabbit cranial sutures in vitro: a new experimental model for studying the response of fibrous joints to mechanical stress.

An organ culture system has been developed whereby mechanical stress can be applied to cranial sutures under controlled experimental conditions. The application of a continuous tensile mechanical stress (30 g) to cranial sutures from newborn rabbits (1--2 days) was accompanied by a significant increase in the incorporation of 3H-leucine and 3H-proline into suture protein. The specific activities of 3H-hydroxyproline indicated that mechanical stress produced a two-fold increase in the incorporation of 3H-proline into collagen. However, the proportion of the total radioactivity recoverable in collagen (45.63 +/- 2.33% for nonstressed; 40.58 +/- 2.17% for stressed sutures) was not significantly different. These data suggest that the increase in collagen synthesis occurs as part of a general stimulation of protein synthesis, and do not support the view that mechanical stress is the principal mechanism regulating the turnover of collagen in fibrous joints. These initial studies demonstrate that an in vitro experimental model has considerable potential for investigating the morphological and metabolic response of fibrous joints to mechanical deformation.

Animals↗
PubMed1978

Neutral metallo-proteinases of rabbit bone. Separation in latent forms of distinct enzymes that when activated degrade collagen, gelatin and proteoglycans.

Rabbit bones in culture produce specific collagenase and neutral metallo-proteinase activity in latent forms that can be activated by either 4-aminophenylmercuric acetate or trypsin. Latent neutral metallo-proteinase activity was resolved by gel filtration into two enzymes, distinct from collagenase, that degrade gelatin and cartilage proteoglycans.

Animals↗
PubMed1975

The influence of function on chondrogenesis at the epiphyseal cartilage of a growing long bone.

In order to study the behaviour of epiphyseal cartilage in a nonfunctional environment, the third metacarpal bone was transplanted intracerebrally as an isograft between 7-day-old litter-mate rats. Host animals were killed 1, 2, 3, 4, 5, 6 weeks post-operatively, and the cellular kinetics evaluated by means of tritiated thymidine autoradiography. The study was also used to compare the effects of function on chondrogenesis at the epiphyseal cartilage with that previously demonstrated for the condylar cartilage of the mandible (Meikle, '73a). Transplantation resulted in three major changes in the cartilage; there was a decreased rate of proliferative activity in the cell columns; the cartilage failed to maintain a satisfactory increase in transverse diameter; the cells of the perichondrium differentiated into osteoblasts instead of chondroblasts. Autoradiographic and histological findings suggested that the inability of the cartilage to increase in transverse diameter was related to the decreased rate of proliferative activity in the cell columns and not to the cessation of perichondrial chondrogenesis. On the basis of these findings two conclusions can be made. 1. Extrinsic mechanical stresses associated with function appear to be necessary for the normal interstitial growth of epiphyseal cartilage during postnatal development, suggesting that functional activity can influence the rate of cell proliferation. 2. Functional activity provides the stimulus for the differentiation of perichondrial cells into chondroblasts.

Animals↗
PubMed1975

The distribution and function of lysosomes in condylar cartilage.

Using electron microscopic and histochemical methods it was possible to demonstrate in condylar cartilage the presence of acid phosphatase and aryl sulphatase in lysosome-like bodies of the cartilage cells, confirming that they are lysosomes. Lysosome-like bodies were also present in the extracellular matrix, but they reacted for acid phosphatase only. Lysosomes extruded by the cells may well provide a means whereby lysosomal enzymes are enabled to take part in the preliminaries to matrix calcification. The large numbers of lysosomes in the hypertrophic chondrocytes, however, are probably more concerned in bringing about autolysis of the cells than in promoting calcification of the matrix.

Acid Phosphatase↗