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PubMed2005

Expression patterns of matrix metalloproteinases and vascular endothelial growth factor during epiphyseal ossification.

UNLABELLED: In situ hybridization studies allowed for the localization of three MMPs and the angiogenic factor VEGF during secondary ossification. MMPs were widely expressed during ossification of the secondary center, whereas expression of VEGF was restricted to later stages. INTRODUCTION: The spatiotemporal expression patterns of the matrix metalloproteinases gelatinase-B (MMP-9), collagenase-3 (MMP-13), and membrane-type 1 metalloproteinase (MMP-14) and the angiogenic peptide vascular endothelial growth factor (VEGF) were studied during development of the proximal epiphysis of the rat tibia. MATERIALS AND METHODS: Cell expression was analyzed by in situ hybridization. Studies on osteoclastic activity, matrix mineralization, cell proliferation, and vascular progression were also performed. RESULTS: MMP-9, MMP-13, and MMP-14 were expressed in discrete perichondrial cells that gave way to sites of intrachondral canal formation. High expression levels for the three MMPs were found at the blind ends of advancing intrachondral canals and at the expanding borders of the marrow space. Signals for MMP-9 and MMP-13 were in close proximity but did not overlap, whereas MMP-14 was expressed in both MMP-9+ and MMP-13+ cells. VEGF was not expressed during formation of intrachondral vascular canals but was observed in hypertrophic chondrocytes during formation of the bone marrow cavity. CONCLUSIONS: Expression of MMPs and VEGF are constant events during development of the secondary ossification center. We propose that MMPs are involved in targeting proteolytic activity during epiphyseal development. VEGF is not expressed during early formation of vascular canals, but it may have a role in the formation of the bone marrow cavity.

Animals↗

PubMed1981

Radiographic studies on maturation process of secondary ossification centers in long bones of the Japanese white rabbit.

The maturation process of the secondary ossification centers of the extremities was radiographically investigated in the Japanese white rabbit of both sexes aged 1 day to 78 weeks. The ossification centers appeared at 1 day of age in the proximal and distal epiphyses of humerus, the head of femur, the distal epiphysis of femur and the proximal epiphysis of tibia, at 1 week of age in the supraglenoid tubercle of scapula, the proximal and distal epiphyses of radius, the proximal and distal epiphyses of ulna, the greater trochanter of femur, the distal epiphysis of tibia and the distal epiphysis of fibula, and at 2 weeks of age in the proximal epiphysis of fibula. The ossification centers developed rapidly from the time of appearance to 8 weeks of age, and gradually thereafter until 32 weeks of age. By 78 weeks of age, the complete fusion with the diaphysis was observed in the supraglenoid tubercle of scapula, the proximal and distal epiphyses of humerus, the head and distal epiphysis of femur. Incomplete fusion, leaving an epiphyseal line, was found in the proximal and distal epiphyses of radius, ulna, tibia and fibula, respectively.

Animals↗

PubMed2001

GH substitution reverses the growth phenotype but not the defective ossification in thyroid hormone receptor alpha 1-/-beta-/- mice.

Thyroid hormone receptor alpha 1, beta 1 and beta 2-deficient mice (TR alpha 1-/-beta-/- mice) demonstrate growth retardation and defective ossification in the epiphyses associated with an inhibition of the GH/IGF-I axis. There are differences between TR alpha 1-/-beta-/- mice (receptor deficient) and the hypothyroid animal model (ligand deficient). Such differences include possible repressive actions exerted by unliganded receptors in the ligand-deficient (hypothyroid) model but not in the receptor-deficient model. In the present study we have investigated whether or not GH substitution rescues the skeletal phenotype of TR alpha 1-/-beta-/- mice. TR alpha 1-/-beta-/- and wild-type (WT) mice were treated with GH from day 18 until 10 weeks of age. GH substitution of mutant mice resulted in a significant and sustained stimulatory effect on the body weight that was not seen in WT mice. GH-treated mutant mice but not GH-treated WT mice demonstrated increased length and periosteal circumference of the femur. However, GH substitution did not reverse the defective ossification seen in TR alpha 1-/-beta-/- mice. TR alpha 1-/-beta-/- mice displayed increased width of the proximal tibial growth plate, which was caused by increased width of the proliferative but not the hypertrophic layer. GH substitution did not restore the disturbed morphology of the growth plate in TR alpha 1-/-beta-/- mice. In summary, GH substitution reverses the growth phenotype but not the defective ossification in TR alpha 1-/-beta-/- mice. Our data suggest that TRs are of importance both for the regulation of the GH/IGF-I axis and for direct effects on cartilage.

Absorptiometry, Photon↗

PubMed1977

Injuries of the medial epicondylar ossification center of the humerus.

The complex nature of the ossification centers makes elbow injuries in a child or adolescent difficult to evaluate. The medial epicondylar ossification center is involved in a significant proportion. Injuries vary from simple avulsions to wide displacement with entrapment in the elbow. When entrapment occurs, it may be mistaken for the trochlear ossification center and the true nature of the injury overlooked. Radiographic findings are presented. The anteroposterior view was found to be diagnostic in minimal or marked avulsions of the medial epicondyle because of the characteristic inferior displacement. The anteroposterior view may not always be diagnostic in cases of entrapment of the medial epicondyle; the lateral view is usually diagnostic. In elbow dislocation, the presence and position of the medial epicondyle must be ascertained. Comparison and oblique views are often of value.

Adolescent↗

PubMed1990

[Matrix vesicles in membranous ossification].

Calcification process in membranous ossification was examined histologically by light and electron microscopies in comparison with that in enchondral ossification. The following results were obtained: 1) In the rat tibial articular cartilage, the extracellular matrix proceeding from the transitional to the hypertrophic zone consisted of the following three layers from the proximal: the first layer in which ruthenium red positive granules were densely populated and thin collagen fibrils diffusely arranged but few matrix vesicles were observed; the second one containing numerous matrix vesicles and slightly thick collagen fibrils; and the last one in which the thick collagen fibrils were observed while matrix vesicles and ruthenium red positive granules were few. 2) In the calcified regions in the extracellular matrix of MC3T3-E1 cells, the regions of alveolar new bone formation due to orthodontic tooth movement and the calcified regions in the interparietal suture expanded mechanically in vitro, the number of matrix vesicles was less than those in the regions of enchondral ossification. 3) Ruthenium red positive granules were fewer in the regions of alveolar new bone formation after the orthodontic tooth movement than in the calcified regions of cartilage. 4) The observation on MC3T3-E1 cells revealed the two different possibilities of the processes of calcification: the calcification induced by matrix vesicles as an initiator and that directly related to mineral deposit on the collagen fibrils.

Alveolar Process↗

PubMed1975

A system of grading ossification in limbs of foals to assist in radiologic interpretation.

Tetracycline-labeled bones of 23 foals from 52 to 104 days old were sectioned and macroscopically examined to assess the extent of ossification or fusion of ossification centers. A grading system was devised with which to record information about the ossification centers and growth plates. The objective was to define anatomic standards which could contribute toward obtaining an accurate radiologic interpretation. Labeled limb bones of 3 neonatal foals were similarly treated, but grading of these was limited to the consideration of whether each site was still cartilaginous or had commenced to ossify.

Age Factors↗

PubMed1992

Scanning electron microscopy of femoral ossification in the human foetus.

The ossification of human femoral bone was studied in 10 fetuses aged from 8 to 40 weeks, and in a 3 1/2 month-old child. After dissection and radiographic examination, each femur was sectioned in a sagittal plane. One part was processed for routine histology, the remaining one for scanning electron microscopy. By comparing the radiographic, light microscopic and scanning electron microscopic pictures, it is possible to precise the pattern of ossification and to define 3 main periods during human fetal development (pure cartilage, metaphyseal and diaphyseal ossification, constitution of a cortex and a medulla in the diaphysis).

Embryonic and Fetal Development↗

PubMed2004

Is the absence of the ossific nucleus prognostic for avascular necrosis after closed reduction of developmental dysplasia of the hip?

The presence of the ossific nucleus before reduction of developmental dysplasia of the hip may reduce the rate of avascular necrosis. Forty-eight hips in 45 children who underwent successful closed reduction had at least a 2-year follow-up. Medical records were reviewed for sex, side, Pavlik harness, traction, age at reduction, adductor tenotomy, cast duration, length of follow-up, and subsequent surgery. Prereduction radiographs were reviewed for presence or absence of the ossific nucleus. Avascular necrosis was noted as present if there was evidence of Bucholz and Ogden type II, III, or IV on the postreduction radiographs. Avascular necrosis was noted postreduction in 17 hips. Adductor tenotomy may reduce the rate of avascular necrosis following closed reduction. Delaying closed reduction until the presence of the ossific nucleus can be detected radiographically may reduce the rate of avascular necrosis. The presence of avascular necrosis increases the need for subsequent surgery.

Female↗

PubMed2004

The ossification of the metacarpal and phalangeal bones in human foetuses.

An evaluation was made of the ossification level of the metacarpal and phalangeal bones in human foetuses of both sexes from the 4th to the 9th month of gestation. Our results indicate that ossification of phalangeal bones 1 to 5 always started at the distal end of the phalanx and endochondral ossification prevailed in the proximal phalanx of the thumb.

Bone Development↗

PubMed1991

Untreated hypophosphatemic vitamin D-resistant rickets with symptomatic ossification of the ligamentum flavum.

An adult case of untreated hypophosphatemic vitamin D-resistant rickets with symptomatic ossification of the ligamentum flavum in the thoracic region is reported and discussed with regard to the calcium metabolism and the ligamentous ossification. Factors influencing ossification of the ligamentum flavum may be mechanical stress on the spine and an increase in calcium retention.

Adult↗

PubMed1991

[Hip and spinal ossification enthesopathies induced by etretinate therapy in peripheral psoriatic arthritis].

The occurrence of ossifying enthesopathy during treatment with synthetic retinoids (etretinate, isotretinoin and acitretin) is a side-effect more and more frequently recorded. The authors report here a new case in a patient with a severe psoriatic arthritis. This observation is characterized by the size of ossifications on hips and lumbar spine which appeared after two years of etretinate therapy. The interest of this observation lies in the fact that ossifications occurred while the patient was treated with long-term corticotherapy. The disease for which retinoids are prescribed does not seem to influence the occurrence of those lesions and it is likely that the responsibility of these molecules is entire. Lesions are enthesitis ossification. They are frequent during these treatments (average of 70%) after an average time of 24 to 36 months for etretinate and of 10 months for isotretinoin. Lesions are asymptomatic in about 50% of the cases. After discontinuation of treatment, lesions become quiescent and does not disappear. Growth hormone or abnormalities in vitamin A metabolism could play a role in the physiopathology of lesions.

Arthritis, Psoriatic↗

PubMedDate not supplied

[Tuberculous spondylitis with syndesmophytes and paraspinal ossification. Two case reports].

The authors described 2 patients with spinal tuberculosis. The first one was presented with multiple anterior marginal involvement of vertebral bodies, centrosomatic spondylitis of L3, associated with a syndesmophytic showing spinal ossification. In the second case, spinal tuberculosis involved the vertebral arc of L2 and L4. A paravertebral ossification on both sides of L4 was seen. The nature of these vertebral and paravertebral ossifications was discussed.

Adolescent↗

PubMed1990

Ossification of the human fetal basicranium.

Previous investigations of prenatal development of the human cranium have not identified the sequence of its ossification. The purpose of the present study was to elucidate the pattern of skeletal maturity of the cranial bones in the midsagittal region anterior to the foramen magnum. This study is based upon a radiographic and histochemical investigation of midsagittal tissue blocks of the cranial bases of 73 human fetuses derived from the first half of the prenatal period. A marked regularity in the ossification pattern of the bones in the midsagittal part of the human cranium was observed. Ossification starts in the frontal bone. The sequence in which the next bones ossify is occipital bone, basisphenoid bone, presphenoid bone, and ethmoid bone. The material was divided into 7 maturity stages devised for this analysis. The stages were related to general fetal size (crown-rump length) and to general fetal maturation (composite number of ossified bones in hand and foot). Skeletal development of the median part of the human cranium is not strictly correlated with the size or the stage of general maturation of the fetuses. Knowledge of normal skeletal development is necessary for understanding anomalies of development.

Bone Development↗

PubMed1989

Radiographic changes in the ossific nucleus in congenital dislocation of the hip.

Twenty one patients with a delayed diagnosis of congenital dislocation of the hip were studied to assess the relevance of radiographic changes in the ossific nucleus of the proximal femur during the first year following treatment. All abnormal hips demonstrated sclerosis of the margins of the ossific nucleus with irregularity of its surface at three months following surgery. In nineteen patients a head within a head was identified. These common changes are interpreted as the radiographic appearance of a spherical growth disturbance line formed by the ossific nucleus. It is concluded that these radiographic changes which are often accepted as indicators of avascularity are of no detrimental significance in the absence of physeal injury.

Epiphyses↗

PubMed1987

Ultrasound evaluation of the distal femoral epiphyseal ossification center as a screening test for intrauterine growth retardation.

In a heterogeneous group of 226 pregnant women, a retrospective study was done of the relation between the distal femoral epiphyseal ossification center detected by ultrasound and the birth weights of the infants. The ossification center of the femur was detectable in 202 of the 208 infants appropriate for gestational age; it was undetectable in 15 of the 18 infants small for gestational age. Because our results compared favorably with those reached by more complicated methods in the literature, we propose that the distal femoral epiphyseal ossification center be used as a screening test for intrauterine growth retardation.

Birth Weight↗

PubMed1987

Heterotopic ossification in hemiplegia following stroke.

Heterotopic ossification is a recognized complication in patients with head injury, burns, paraplegia, or direct trauma to muscle tissue. Heterotopic ossification with hemiplegia following stroke is considered rare. A case of a 53-year-old patient with right hemiplegia who developed painful right hip, limiting range of movement and progress in ambulation, is presented. X-ray and laboratory tests confirmed the presence of heterotopic ossification, suggesting that this condition may not be so rare in patients with a cerebrovascular accident, but may escape recognition, with pain being considered to stem from soft-tissue strain, premorbid arthritis, or altered sensation commonly associated with stroke.

Cerebrovascular Disorders↗

PubMed1983

[Determination of sex differentiated ossification patterns of costicartilage pairs II to VI: post mortem study of radiograms of the anterior chest wall].

On the basis of widely laterally resected anterior chest walls, ossification specimens of femal (n = 95) and male (n = 112) individuals of different age have been examined. An unexpected high significance of the already described sex-dimorphism could be secured between the 20th and 50th year of age. The estimated epiphenomenological changes impress as a female calcification type with centrally in the costal cartilage situated ossifications and as a male calcification type with sheath-like calcifications situated at the cranial and caudal edge of the costicartilage. Isolatedly observed contra-sexual ossifications specimens are expressively hinted at.

Adult↗

PubMed1993

Skeletal dysplasia in perinatal lethal osteogenesis imperfecta. A complex disorder of endochondral and intramembranous ossification.

Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis.

Bone Diseases, Developmental↗