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[Morphologic studies of the beginning of vascularization and ossification in human thyroid cartilage].

In contrast to the cartilaginous preformed bones of the skeleton, ossification of human thyroid cartilage begins at the end of the second decade of life. The process continues until an advanced age and shows sex differences. An in-growth of blood vessels by cartilage canals is a prerequisite for ossification. The aim of the study was to investigate the temporal and spatial appearance of cartilage canals in thyroid cartilage. Extracellular matrices of cells in cartilage canals were characterized immunohistochemically. Corrosion casts indicated that the cricothyroid branch of the superior thyroid artery was involved in vascularization of the thyroid cartilage. The first cartilage canals were detectable at the end of puberty, always lying at certain distances to almost ossified areas of the thyroid cartilage. The extracellular matrix localized at the border of the cartilage canals reacted with antibodies against type I collagen and type III procollagen, as well as with antibodies against type II collagen. This finding suggests that these cells are intermediate between fibroblasts and chondrocytes.

Adolescent↗

X-ray densitometry applied to the study of prenatal ossification.

To evaluate bone mass (BMC) and bone density (BMD) it is possible to utilize x-ray absorptiometry. This method is usually employed in clinical practice for the evaluation of metabolic osteopathies. The authors describe an application of this diagnostic technique to the study of the ossification pattern of the human vertebral column in pre- and post-natal life. On this regard, an ultra high resolution software allowed to analyze quantitative aspects of the ossification of small size vertebral bodies by lateral scans directly performed on bone specimens.

Absorptiometry, Photon↗

Contribution to the study of the development and ossification of human sternum.

We have studied the development of sternum in man. Complete microscopic series of sections through thorax of human embryos and fetuses from the second and third months of gestation served as the research material. Preparations were stained by Alcian blue and Mayer's haematoxyline, counterstained by eosine. We also had a set of macroscopic preparations of sterna and adjacent parts of ribs from fetuses of the fifth and sixth months of gestation. These specimens were stained by Alcian blue and by Alizarine and subsequently cleared by glycerine method. We have found that sternum develops by a fusion of sternal bars. Sternal bars develop from anterior bent parts of ribs, lying one over another like tiles. The newly formed sternum has different proportions in comparison to its definitive state. In all the cases its manubrium is wider and bigger, its xiphoid process is longer, in almost all the cases doubled or at least bifurcated. The sternocostal junctions are provided with interzones with the exception of the first rib. Its primordium continues into sternum without any border. Clavicle is connected with sternal anlage without any visible border and this interzone quickly develops as the primordia of the sternoclavicular articulation and the disc. In the medial part, there is a cartilaginous model which ossifies very early--as the first bone of the body. In young embryos from the end of the second month of gestation the clavicle and sternum show very different structures. Ossification of the sternum begins in the fifth month by developing a large number of very small centers of ossification which are not yet detectable by X-ray or CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[New method for evaluating ossification of the carpal bone. From a study with 5225 Spanish children].

The author present a new method of assessment of bone age derived from the analysis of carpal osseous development of 5,225 Spanish children and adolescents. The method is based upon the determination of a carpal index from the measurement of the largest diameter of the eight carpal bones, the proximal epiphysis of the first metacarpal and the distal cubital and radial epiphyses. There is a highly significant correlation of this carpal index with chronological age (P < 0.0001). From this index the author has set up an equation defining an index of evaluation of carpal ossification which helps to estimate bone age according to six different ranges of significance: significant retardation, moderate non significant retardation, borderline normality, complete normality, moderate non significant advance, significant advance. The method is simple to realize. It reduces the risk of errors in the evaluation of bone age due to asynchronisms of maturation of the ossification centres and to the individual subjective factor occurring with a morphologic assessment. Furthermore it takes into account the physiological variations of bone age on both sides of the mean normal value.

Adolescent↗

Disodium etidronate in the prevention of postoperative recurrence of heterotopic ossification in spinal-cord injury patients.

Disodium etidronate was used in a clinical trial with four patients to study its effectiveness in preventing the recurrence of mineralization after surgical removal of heterotopic ossification. These patients, who had sustained injuries to the spinal cord followed by anklysos of the hip, had seven surgical wedge resections as part of a controlled or double-blind study. Roentgenograms showed that in the resections done without the drug there was recurrence within three weeks, whereas with the drug there was no sign of recurrence as long as the drug was administered. After discontinuation of drug therapy, recurrence was variable but less than expected. Disodium etidronate is the first therapeutic agent which may delay and partially prevent postoperative recurrence of heterotopic ossification.

Adult↗

Development of the cartilage canals and the secondary center of ossification in the distal chondroepiphysis of the prenatal human femur.

The cartilaginous epiphysis of the distal femur is vascularized by a network of cartilage canals during prenatal development. The vascular invasion of the epiphysis begins at approximately eight to ten weeks of gestation with the initiation of cartilage canal formation. A complex vascular system develops within the canals and is well defined by fourteen weeks of gestation. The vascular system is fully developed several months prior to the development of the secondary center of ossification. The formation of the secondary center of ossification within the distal femoral epiphysis is preceded by changes that occur simultaneously within both the chondrocytes in the central portion of the epiphysis and the vascular and perivascular elements contained within the cartilage canals in the central portion of the epiphysis. These concurrent changes in the cellular morphology of the central chondrocytes and in the cellular structure of the central cartilage canals appear to be linked with the initiation of the process of osteogenesis.

Cartilage↗

Specific collagen mRNAs elucidate the histogenetic relationship between the growth plate, the tissue in the ossification groove of Ranvier, and the cambium layer of the adjacent periosteum. A preliminary report.

In situ hybridization was employed to study cellular phenotypes in the ossification groove of Ranvier in young rabbits. The expression of Type II collagen mRNA was seen in chondrocytes in all layers of the growth plate. Messenger RNA for the cartilage-specific Type II collagen was also detected in cells of the inner layer in the ossification groove and of the cambium layer of the adjacent periosteum, providing strong evidence for the views of Ranvier that these cells originate in the growth plate. These findings modify the interpretation of the pathogenesis of diseases of the growing skeleton.

Animals↗

[The effect of the ossification processes of the hyoid bone and laryngeal cartilages on the formation of injuries to the organs of the neck].

Effects of ossification processes on the incidence and specific features of injuries to sublingual bone, thyroid and ring-like cartilages were studied by stereomicroscopy of the skeletal preparations of these anatomical formations for the first time. The results of examination of cases with hanging permit us doubt the opinion universally acknowledged in forensic medicine that the possibility of injuries of the sublingual bone and laryngeal cartilages increases with their ossification.

Asphyxia↗

Advanced cervical spondylosis with ossification into the posterior longitudinal ligament and resultant neurologic sequelae.

Advanced cervical spondylosis (ACS) with ossification of the posterior longitudinal ligament (OPLL) may be distinguished from classical OPLL on magnetic resonance- and computed tomography-based studies by the presence within the hypertrophied posterior longitudinal ligament (PLL) of segments of punctate calcification-ossification. Between 1989 and 1993, 50 patients with an early form of classical OPLL, variably associated with ACS, had cervical surgery. Averaging in their mid-40s in age, and exhibiting signs of radiculopathy or myeloradiculopathy, patients were uniformly managed with anterior surgical decompression and fusion. The average follow-up interval was 38 months (range 18-66 months). In select patients, early OPLL coexisted with classic OPLL. ACS with OPLL may represent an early form of the generation of classic OPLL in younger symptomatic individuals, which may be successfully addressed with an anterior surgical approach.

Adult↗

Collagenase-3 (MMP-13) is expressed during human fetal ossification and re-expressed in postnatal bone remodeling and in rheumatoid arthritis.

To explore possible physiologic functions for the metalloproteinase collagenase-3, we have examined its temporal and spatial expression during human fetal development. Except for mesenchymal cells in the umbilical cord at 4 weeks of gestation, signal for collagenase-3 mRNA was confined to mineralizing skeletal tissue and detected in hypertrophic chondrocytes and osteoblastic cells involved in ossification beginning at 10 weeks and continuing through gestation. These cells were also immunoreactive with collagenase-3 antiserum, indicating their ability to produce collagenase-3 protein. In osteoblastic cells, the expression of membrane-type 1 metalloproteinase and 72-kd gelatinase mRNA, which have the capacity to activate collagenase-3 in vitro, colocalized with that of collagenase-3. In postnatal tissues, collagenase-3 was re-expressed in processes involving skeletal remodeling, such as bone cysts and ectopic bone and cartilage formation. Multinucleated osteoclasts were consistently negative for collagenase-3. Furthermore, in patients with seropositive rheumatoid arthritis, expression of collagenase-3 was prominent in articular cartilage, and collagenase-3 protein was detected by immunoblotting in synovial fluids. Consistent with its substrate specificities, a plausible function for collagenase-3 in these processes is to preferentially degrade type II collagen, thus serving a role during primary ossification, in skeletal remodeling, and in destructive joint disease.

Aged↗

[The secondary ossification center of fetus].

Most textbooks on human anatomy and human embryology state that the appearance of the secondary ossification center (SOC) of the fetus is considered to be after or around birth. In our study, while collecting the data on growth indexes from 346 fetuses in normal pregnancy with conceptional ages from 12 to 38 complete weeks, we investigated using B-ultrasonography the appearance of the secondary ossification center and compared them in part with the anatomically observed data collected from fetal specimens. The results of B-ultrasonic observation show that SOC can be seen at the distal end of femur after 29 complete weeks. From them on, the percentage of the appearance of SOC increases weekly, and it is almost 100% in 34 complete weeks.

Female↗

[Ultrasonography assessment of ossification foci of the wrist and pubertal growth spurt].

High-resolution ultrasound (US) of the hand and wrist was compared with radiography in 26 young patients (mean age: 11.4 years) to be submitted to orthodontic therapy. US scans were targeted on the ossification centers critical for the growth spurt, namely the pisiform and adductor sesamoid bones of the metacarpophalangeal joint of the thumb and the cartilage of the distal phalanx of the third finger. All images were retrospectively reviewed on a double-blind basis by two independent observers who gave a conspicuity score to each structure of interest. All the scores were submitted to statistical analysis with the Wilcoxon test. US images clearly demonstrated the initial appearance of the ossification centers of the pisiform and sesamoid bones. These structures appeared as hyperechoic spots causing marked acoustic shadowing. The persistence of the phalangeal cartilage was depicted as a thin rim interrupting the hyperechoic cortical profile of the bone. US results were statistically equivalent to radiographic findings in the pisiform [p (op1) = .3105; p (op2) = .8886] and sesamoid bones of the thumb [p (op1) = .1386; p (op2) = .354]. A statistically significant difference between the two techniques was found in the third finger cartilage (p (op1) = .0277; p (op2) = .0759) because its profile was poorly depicted on some US images. To conclude, wrist US is proposed as a simple and valuable radiation-free support examination for the follow-up of skeletal maturation in adolescents to be submitted to orthodontic therapy.

Adolescent↗

Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To clarify this mechanism, we investigated the effects of in vitro cyclic stretch (120% peak to peak, at 0.5 Hz) on cultured spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non-OPLL cells) patients. The mRNA expressions of Cbfa1 (an osteoblast-specific transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. The effects of cyclic stretch on the spinal ligament tissues derived from OPLL and non-OPLL patients were also analyzed by immunohistochemistry using an antibody against Cbfa1. The expression of Cbfa1 was increased by cyclic stretch at the center of the spinal ligament tissues of OPLL patients, whereas no change was observed in the tissues of non-OPLL patients. Furthermore, U0126, a specific inhibitor of MAPK kinase (MEK), suppressed the stretch-induced mRNA expressions of Cbfa1, ALP and type I collagen in OPLL cells. These results suggest that in OPLL cells, mechanical stress is converted by integrin beta1 into intracellular signaling and that Cbfa1 is activated through the MAP kinase pathway. Therefore, we propose that mechanical stress plays a key role in the progression of OPLL through an increase in Cbfa1 expression.

Aged↗

Dietary habits and risk of ossification of the posterior longitudinal ligaments of the spine (OPLL); findings from a case-control study in Japan.

The relation between dietary habits and the risk of ossification of the posterior longitudinal ligaments of the spine (OPLL) was investigated in a case-control study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were identified and individually matched by age and sex with community controls (n = 138) randomly selected from the general population in Hokkaido. A self-administered food-frequency questionnaire was used to assess habitual dietary intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated, using conditional logistic regression models to compute the OR adjusted for a history of diabetes mellitus. We found that frequent consumption of pickles (salted products) was significantly associated with an increased risk of OPLL, with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI, 0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our findings suggest that dietary habits may constitute independent risk factors for OPLL. Further studies will be needed to prospectively determine the relationship between dietary habits and OPLL risk.

Adult↗

Secondary medulla oblongata involvement following middle cervical spinal cord injury associated with latent traumatic instability in a patient with ossification of the posterior longitudinal ligament.

STUDY DESIGN: A case report. OBJECTIVES: To report a rare case of extension of edema and hemorrhage from initial C4-5 spinal injury to the medulla oblongata. SETTING: Center for Spinal Disorders and Injuries, Bibai Rosai Hospital, Japan. METHODS: A 68-year-old man with ossification of the posterior longitudinal ligament (OPLL) had sustained tetraplegia after tumbling over a stone. Initially, the patient was diagnosed with an acute C4-5 spinal cord injury without radiological abnormalities and was treated conservatively. At 7 h after the injury, the patient had an ascending neurological deficit, which required respiratory assistance. Magnetic resonance imaging revealed a marked swelling of the spinal cord above C4-5 extending to the medulla oblongata. RESULTS: Retrospective radiological assessment revealed that the spine was unstable at the injury level because of discontinuities in both anterior and posterior longitudinal ligaments. There was also signal intensity change within the retropharyngeal space at the C4-5 intervertebral disc. This injured segment was highly vulnerable to post-injury dynamic stenosis and easily sustained secondary neural damage. CONCLUSIONS: This case report emphasizes a careful radiological assessment of latent structural instability in patients with OPLL in order to detect and prevent deteriorative change in the spinal cord.

Aged↗

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

Sleeping habit and other life styles in the prime of life and risk for ossification of the posterior longitudinal ligament of the spine (OPLL): a case-control study in Japan.

BACKGROUND: Although the average age of onset of ossification of the posterior longitudinal ligament of the spine (OPLL) is at around 50 years, the onset of the symptoms is insidious and the progression is very slow. The etiology of OPLL has not been elucidated in detail. Previous studies have suggested that a high-salt diet and low consumption of animal protein, glucose intolerance and high body mass are risk factors for OPLL. However, there is little information about the relationship between OPLL and life styles in the prime of life (between 30 and 50 years). METHODS: To facilitate early prediction and prevention of OPLL, we analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol drinking and hangover in subjects in the prime of life. Self-administered questionnaires were obtained from patients with OPLL and their sex- and age-matched controls. Sixty-nine patients diagnosed with OPLL within 3 years previously and 138 sex- and age-matched controls without backbone diseases, randomly selected from participants in a health checkup in a local town, were enrolled. RESULT: Moderate amount of sleep (6-8 hours vs. 5 hours or shorter and 9 hours or longer; odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06, 0.54) and a regular sleeping habit (i.e., going to bed and getting up at regular time) (OR=0.44, 95% CI=0.22, 0.90) were associated with a decreased risk of OPLL even after adjusting for other factors. On the other hand, moderate physical exercise (once a week or more v.s. less than once a week: OR=0.97, 95% CI=0.42, 2.26), smoking (OR=1.41, 95% CI=0.67, 2.97), drinking (OR=1.08, 95% CI=0.53, 2.20) and hangover (OR=1.12, 95% CI=0.43, 2.94) in the prime of life showed no correlation with risk of OPLL. CONCLUSION: Good sleeping habits in the prime of life may decrease the risk of OPLL.

Activities of Daily Living↗

[Posterior longitudinal ligament ossification: case report].

Posterior longitudinal ligament ossification of cervical spine is a rare condition among caucasians. A 42 years old japanese patient with progressive walking difficulty was diagnosed with this pathology by CT scan and MRI and treated surgically by an anterior approach with arthrodesis. Pathophysiology, racial prevalence, clinical picture, radiological characteristics and surgical approaches options are revised.

Adult↗