Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF)
Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged
Aims. This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX)
Aims. Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in
Objectives. This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female
Aims. Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Methods. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of
Aims. Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods. A total of 18 eight-week Sprague-Dawley
Objectives. Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Methods. Closed transverse fractures were created in the femurs of 116
Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar
Aims. The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods. Sprague-Dawley
Aims. To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods. A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results. The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15
Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX
Objectives. Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX)
Objectives. Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in
Objectives. Electromagnetic fields (EMF) are widely used in musculoskeletal
disorders. There are indications that EMF might also be effective
in the treatment of osteoporosis. To justify clinical follow-up
experiments, we examined the effects of EMF on bone micro-architectural
changes in osteoporotic and healthy
Objectives. Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. Methods. Female Wistar
In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of
Aims. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods. Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in
We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi
We investigated the effect of progesterone on the nerve during lengthening of the limb in
Using a rat model the characteristics of the sensory neurones of the dorsal-root ganglia (DRG) innervating the hip were investigated by retrograde neurotransport and immunohistochemistry. Fluoro-Gold solution (FG) was injected into the left hip of ten
1. Into osseous defects cut in the pelvis of
Apart from preliminary notices of present work, previous reports of experimental and clinical trials of the effects of a high-peak pulsed electromagnetic field (PEMF) on degeneration and regeneration of peripheral nerves lacked statistical analysis. Therefore, we designed experiments with standardised operative, histological, cytological and morphometric techniques to assess the effect of PEMF on lesions of the common peroneal nerves in paired male
1. In growing
1. Experimental arthritis was induced in
1. The distribution of isotope following a single injection of either Ca. 45. or C. 14. -proline has been studied in young
The parameters of cellular proliferation and growth in the growth plates of immature
The right sciatic nerve of 50 one-month-old male
1. Dislocation and subluxation of the hip has been produced in young
1. A method of constricting sciatic nerves of
An orientated substratum has been implicated in the development and regeneration of axons and synapses. We prepared a basement membrane matrix from autogenous striated muscle, used it to repair the sciatic nerve in
After the simultaneous administration of radiocalcium and radiophosphorus to young
1. An experimental study of the healing mechanism in circumscribed defects in femora of albino
1. Some physical properties of living and dead bone have been studied in
We examined the cellular responses to various particles injected into the knees and the intramedullary femoral cavities of
Continuous strontium administration first induces typical "rickets" in young
We have studied the effect of hydroxyapatite (HA) coating in 15 ovariectomised and 15 normal
The main findings in this experimental work on
It has been shown in experimental animals that the living cells in a bone autograft can make an important contribution to osteogenesis. However, some common clinical techniques, such as the topical use of antibiotic powders on grafts or on the graft bed, are likely to damage or kill the cells. In this experimental study in
Based on a study using a retrograde neurotracer, we have previously found that the dorsal portion of the L5/6 disc in the rat is multisegmentally innervated by dorsal root ganglia (DRG) from the level of T13 to L6, and that sensory nerve fibres from DRG of T13, L1 and L2 pass through the paravertebral sympathetic trunks. In this study in newborn
Revascularisation of syngeneic and allogeneic intramuscular bone grafts have been studied using radioactive microspheres to measure the ingrowth of blood vessels. New bone formation and resorption were measured by 85strontium uptake and by graft weight reduction. Revascularisation, and mineralisation rate were significantly higher in syngeneic grafts than in allogeneic grafts at two, three and six weeks after implantation. The syngeneic grafts lost weight faster indicating that the allogeneic grafts resorbed more slowly. The ingrowth of new vessels is impaired in allogeneic bone, and this probably inhibits the rate of bone formation and resorption of the grafts.
We examined solvent-dried, gamma-irradiated (SD-R) allografts and fresh-frozen (FF) allografts mechanically and morphologically. Before transplantation, FF grafts were more than six times stronger than SD-R grafts. After four weeks, the tensile strength was about the same in both groups. At 24 weeks only collagen fibrils of small diameter were observed in the SD-R grafts while in FF grafts fibrils of small and intermediate diameter were seen. Clinically, we suggest that SD-R grafts could be used as a favourable alternative to FF grafts if care was taken regarding their initial mechanical weakness.
1. The radiographs of paired living and dead rat tibiae, obtained in an experiment previously reported, have been examined by densitometry. 2. The dead bone became progressively less dense than the living bone as the duration of the implantation increased. 3. The change in density was related to the quantity, but not to the quality, of the bone tissue examined.
1. The results of the present investigation indicate that in the foetal rat the juxta-epiphysial vascular bed consists of a dense irregular network of sinusoids in direct contact with the growth cartilage, supplied by end-arteries, and drained by a profusion of metaphysial sinusoids. 2. The circulation is a closed one–that is, the endothelium is unbroken in its continuity and microhaemorrhages do not occur against the cartilage. 3. It is possible that juxta-epiphysial endothelial cells or their derivatives are chondrolytic, and that they participate directly, together with other mesenchymal derivatives, in the removal of cartilage as a preparatory stage in enchondral bone formation.
One of the aims of this work was to find criteria by which the quality of bone as a supporting tissue might be judged. This inevitably involves discussion and, if possible, assessment, of the relative importance of the inorganic and organic material of the bone. It is relatively easy to measure the mineral content, and for that reason it has always received more than its due share of attention. In the present experiment the composition of the ash of all bones was remarkably constant, with a Ca/P ratio of 2. Furthermore, X-ray crystallography showed that the structure of the inorganic material was the same in all cases. The great difficulty of measuring variations in the quality of the organic material which is, of course, protein in nature makes it impossible to say how much it influences bone strength. Since at least 40 per cent. of the bone is collagen, either a quantitative or a qualitative alteration might alter bone strength. X-ray crystallography revealed no qualitative differences in the collagen material of bones of the three groups; so that for the present it would seem safer to assume that alterations in the physical properties of the bones are due to variations in the relative proportions of organic and inorganic constituents (Dawson 1946, Bell These experiments show that the three diets produce highly significant differences in the percentage of ash, in SB, and in E. It is possible that some variations in the percentage of ash are due to variations in the absolute collagen (weight of collagen in unit volume of bone substance); but the range of variation in the percentage of ash leaves no reasonable doubt that differences in percentage ash between the diet groups are due essentially to differences in absolute ash. Presumably the collagen contributes something to the strength of the bone; but the indications are that it plays a minor part and that the relative weakness and flexibility of rachitic bones is due to decrease in the absolute ash content. Within any one diet group, the relation between percentage ash and the other two variables, SB and E, is masked by other sources of variation such as those associated with the many measurements involved; and thus the correlation between percentage ash and SB, and also between percentage ash and E, is not significant. At first sight, the scatter diagrams (Figs. 5 and 6) appear to indicate a correlation between ash and SB, and between ash and E. Closer inspection shows, however, that the apparent trend is due largely to differences between the means of the diet groups, and that the points within any one group show no such obvious trend. Figure 7 shows that the position with regard to correlation between SB and E is very different. Here there is an obvious trend within each diet group; the amount of scatter is very much less. Calculation shows that, even when the differences between the means of diet groups is excluded, there is still a significant correlation between SB and E. The question of the correlation between the three variables is discussed more fully in the addendum to this paper. Although the "goodness" of a bone is usually judged by its breaking stress, the experimental findings recorded above suggest that it may be assessed equally well on the basis of elastic properties as shown by Young's modulus. Normal bones, group S in these experiments, were elastic up to 79 per cent. of their breaking stress (Table II): the poorer bones of groups R and N were, however, only a little inferior in this respect. In some cases there was no apparent deviation of the load-deflexion curve from a straight line until the bone was about to break. Such a curve was published in the first paper of this series (Bell, Cuthbertson and Orr 1941), but in the light of further experience this curve is scarcely typical. The terminal falling over of the curve is illustrated in Figure 4 and is much more marked in the bones of group R. While stress at the upper limit of elasticity varies over a wide range in the three groups (Table II and Fig. 4), the strain at this point is remarkably constant at about 1·5 per cent. This same percentage displacement must occur between the molecules of the bone material at the elastic limitâand it may be that, up to this amount of molecular displacement, the deformation is reversible; but that beyond it, plastic changes occur. We have no evidence as to whether the limiting displacement concerns mineral or protein constituents of the bone, or both. We have already commented on the remarkable strength of bone material (Bell While Young's modulus is of interest, both on its own account and as an index of the quality of the bone, its close association with breaking stress suggests that it might be used to predict the maximum load which a bone can carry safely. Since E, unlike SB, can be measured without damage, useful information might be gained by measuring the elasticity of living human bones.
Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles.
1. The process of repair after fracture of the humerus of the growing rat has been studied by histological, histochemical and biochemical methods. 2. Both periosteal and surrounding mesenchymal cells take part in the process of repair. 3. The primary framework of collagen bridging the gap is mainly formed by the mesenchymal cells, while calcification and ossification of the framework is largely a function of the periosteum. 4. The mucopolysaccharide content rises rapidly in the first week after injury, and is followed by a rise in the collagen content during the second week. The deposition of calcium phosphate during the third and fourth weeks causes an apparent fall in the collagen content during that period. The collagen content tends to return to normal during the phase of remodelling in the fifth and sixth weeks. 5. The tensile strength of the healing bone bears a close relation to its collagen content.
Cartilage formation was provoked in the skull vault of the young rat by making multiple incisions, and scraping the periosteum to reduce the blood supply to the injured area. The hypothesis that ischaemia induces osteogenic cells to produce cartilage in the course of fracture repair thus receives experimental support.
1. It has been shown that in experimental rickets the well known changes in the epiphysial cartilage which so seriously affect growth are accompanied by severe interference with the progress of the metaphysial vessels into the growth cartilage. 2. Further evidence has been found that, by the repeated increase in their number, the cartilage cells occupying the more distal part of the proliferative segment become more and more affected by their remoteness from the epiphysial vessels, which supply the transudates to these cells. At a given distance these cells are affected and change, becoming hypertrophic, with increasingly large vacuolae, and are rich in glycogen and alkaline phosphatase. 3. The hypertrophic cells alter the nature of the intercellular substance they deposit and this becomes calcifiable. Provided that the metaphysial vessels are situated at an appropriate distance–about three cell capsules away–and that the blood has its necessary components, calcification occurs. 4. Calcification produces the advancing, rigid multitubular structure within which the progressing metaphysial vessels are protected. 5. The interruption of calcification by the withdrawal of fat-soluble vitamins breaks down the whole mechanism of growth and stops the vessels growing into their proper position. The administration of the required vitamins re-establishes the normal sequence of events and allows the vessels to play their decisive role in osteogenesis. 6. Any mechanism which causes the interruption of the vascular progression, whether from metaphysial ischaemia (Trueta and Amato 1960), from severe pressure (Trueta and Trias 1961) or from lack of calcification by withdrawing the fat-soluble vitamins, equally interrupts growth.
Aims. The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Methods. Female Sprague Dawley (SD)
