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Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast-like cells.

Physiological and pathological observations indicate that basic fibroblast growth factor (bFGF) is an important regulator of osteoblastic cell differentiation and in particular of cranial ossification. Experimental evidence suggests that inorganic phosphate (Pi) transport could be an important function of bone matrix calcification. In the present study, we address the influence of bFGF on Pi transport activity in MC3T3-E1 osteoblast-like cells derived from mouse calvaria. The results indicate that bFGF is a potent and selective stimulator of sodium-dependent Pi transport in these cells. The change in Pi transport activity induced by bFGF depends on transcription and translation and corresponds to a change in the maximum velocity of the Pi transport system (Vmax). These observations suggest that enhanced Pi transport activity in response to bFGF may result from insertion of newly synthesized Pi transporters into the plasma membrane. A selective inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase, SU5402, blunted the stimulation of Pi transport induced by bFGF. It also prevented the increase in protein tyrosine phosphorylation induced by bFGF, including phosphorylation of FGFR-1, FGFR-2, phospholipase C-gamma (PLC-gamma), and Shc as well as the recruitment of the Grb2/Sos signaling complex. In addition, bFGF-induced the activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and p38, effects that were prevented by SU5402. Both the protein kinase C (PKC) inhibitor calphostin C and PKC down-regulation suppressed the stimulatory effect of bFGF on Pi transport. Selective inhibitors of ERK and p38 MAP kinases slightly reduced this cellular response with a significant effect observed with the highest concentration of the p38 MAP kinase inhibitor. In conclusion, the results of this study indicate that bFGF selectively stimulates Pi transport in calvaria-derived osteoblastic cells. The main signaling mechanism responsible for this effect involves tyrosine phosphorylation of PLC-gamma and activation of PKC, with a possible contribution of the p38 MAP kinase pathway.

3T3 Cells↗

[Surgery of multi-sutured craniosynostosis in childhood].

According to own critical experience with the treatment of craniosynostoses (1954-81), using various methods from partial morcellement to total ablation of the cranial vault, the author applied (1982-2000) compound surgical decompression in 40 cases of turricephalic craniostenosis due to multisutural craniosynostosis. The surgical approach to the problem was supported by pre- and postoperative observations of computed three-dimensional bone reconstruction, furthermore by investigation of alterations of SPECT detecting the critical areas of most pronounced intracranial tightness of the skull leading to localized and general cerebral blood flow impairment of the developing brain. The application of newer diagnostic methods contributed to deeper understanding of mechanisms concerning neurodevelopmental retardation and behaviour or defect, disturbances as epilepsy, cranial nerve palsy, spastic paresis, hypothalamic-pituitary insufficiency or poor intelectual performance. This made the possible treatment of preoperative clinical symptoms more efficient. By an early operation we solve the disproportion between the too small skull volume limited by premature ossification of sutures which resulted previously in compression of the growing in size, of the maturing brain. In cases of more complex pathology orbitotomies, with a reconstructive advancement of the orbital rim and maxillas should be performed with multidisciplinary cooperation.

Adolescent↗

Histopathology of the temporal bone in osteogenesis imperfecta congenita: a report of 5 cases.

The histopathologic findings in 8 temporal bones from 5 patients with osteogenesis imperfecta congenita are reported. The otic capsule, bony walls of middle ear, and ossicles showed evidence of both deficient and abnormal ossification. Microfractures were found in the otic capsule and in the anterior process and handle of the malleus, in addition to their common location at the crura of the stapes. The cochlear and vestibular end-organs appeared normal. Pathologic changes compatible with otosclerosis were not seen. The possible implication of these changes on hearing and balance is discussed.

Ear, Inner↗

Collagen types VIII and X, two non-fibrillar, short-chain collagens. Structure homologies, functions and involvement in pathology.

Collagens can be divided into two groups, i.e., fibrillar and non-fibrillar collagens. Short-chain collagens, a subgroup of non-fibrillar collagens, comprises collagen type VIII and type X. These two collagen types show several similarities in structure and possibly also in function. Type VIII collagen appears to be secreted by rapidly proliferating cells. It can be found in basement membranes and may serve as a molecular bridge between different types of matrix molecules. In different tissues this collagen type may serve different functions. Stabilization of membranes, angiogenesis, and interactions with other extracellular matrix molecules. Since collagen type X is produced by hypertrophic chondrocytes, this collagen type can only be found in matrix of the hypertrophic zone of the epiphyseal growth plate cartilage. Collagen type X is probably involved in the process of mineralization, endochondral ossification, and is also proposed to play a role in angiogenesis. Collagen types VII and X may be involved in matrix and bone disorders. Their structure, function, and involvement in pathology are discussed in this review.

Animals↗

[Traumatic myositis ossificans. Posttraumatic non-neoplastic heterotopic ossification].

Myositis ossificans traumatica (MOT) is a nonneoplastic, heterotopic ossification of soft tissues i.e. skeletal muscle, tendons, aponeuroses and fascia. It is often encountered in young male athletes participating in contact sports as a result of a single or repeated contusion. MOT tends to be solitary, localized and well circumscribed with a self-limited growth potential that may culminate in regression. The pathogenesis of MOT is still enigmatic. Recent animal experiments have led to a theory that mesenchymal connective tissue cells, undergo metaplasia induced by trauma and probably osteogenic proteins, to fibroblasts and osteoblasts. These cells deposit and structure osteoid centripetally in the lesion. As the lesion matures, cancellous bone develops into mature, lamellar bone in the periphery of the lesion. In its earlier stages MOT is easily cytologically and radiologically confused with osteogenic sarcoma. The management of MOT is largely conservative and the principles are of considerable value to physicians and physiotherapists engaged in the treatment of sports injuries. This article reviews the various forms of myositis ossificans as well as the pathology, diagnosis and treatment options.

Adolescent↗

Early ossification within the human fetal otic capsule: morphological and microanalytical findings.

Besides the use of conventional techniques such as light and polarization microscopy, the present paper proposes the combined use of transmission electron microscopy, secondary and backscattered electron imaging, energy dispersive X-ray analysis and computed tomography for the diagnostic evaluation of ear pathology in the human fetus. These methods were used to revisit the primary calcification front of the fetal otic capsule between 16 and 23 weeks gestational age. Ultramicroscopic evaluation demonstrates similar fetal bone formation to that found in other bones of the human fetus. The formation of the endosteal and periosteal layers is a typical example of early intra-membranous ossification. The enchondral layer is made up of fibrillar bone, laid down around the calcified cartilage remnants. Microchemical analysis indicates a significantly higher Ca/P ratio in the endochondral layer with respect to the endosteum and periosteum. The consequences of a lower Ca/P ratio in the endosteal layer are discussed in view of calcium homeostasis and inner ear function.

Ear Cartilage↗

Effects of naproxen on connective tissue changes in the adjuvant arthritic rat.

The Freund's adjuvant-injected rat shares a number of features with the arthritis patient, viz the presence of a proliferative synovitis, joint swelling, and cartilage and bone erosion. Naproxen, a prostaglandin synthetase inhibitor which is an effective antiinflammatory agent in laboratory animals and humans, was evaluated as an inhibitor of connective tissue destruction in this model by use of radiologic and histopathologic analyses. Sixteen days after rats were injected with Freund's complete adjuvant, marked joint swelling was noted. On day 17, vehicle or naproxen, 7 mg/kg/day, was administered orally. Twenty-eight days later vehicle-treated animals demonstrated the following pathologic changes in their hindpaws; swelling, cartilage loss, large amounts of pannus within the joint spaces, osteoporosis, bone erosions, periosteal new bone formation, heterotopic ossification, and bony ankylosis. Rats treated 28 days with naproxen had significantly milder disease than the vehicle controls. The incidence of severe juxtaarticular bone destruction was 10/10 in the vehicle controls versus 2/10 of the drug-treated group (P less than 0.01). A comparable reduction in cartilage erosion, incidence of pannus, and new bone formation was noted in the drug-treated group. These effects may relate to an inhibition of prostaglandin biosynthesis; prostaglandins have been shown to: 1) stimulate collagenase secretion from macrophages, 2) stimulate bone resorption in vivo and in vitro, and 3) diminish proteoglycan synthesis in cartilage.

Animals↗

Rickets on MR images.

BACKGROUND: The pathologic changes at the physis in patients with rickets have been well demonstrated histologically. Radiographs can depict only the associated osseous abnormalities. PATIENTS AND METHODS: We report two children in whom MR imaging demonstrated rachitic changes in the physeal cartilage beyond the well-recognized bony features. RESULTS: The striking appearance of the physes and the physes of the secondary ossification centers confirm that MR imaging can successfully evaluate the cartilaginous structures of the developing skeleton. CONCLUSION: Though MR imaging is clearly unnecessary for the diagnosis of rickets, it is important that the typical features are not misinterpreted as other pathology.

Bone and Bones↗

Spinal arachnoiditis ossificans: report of three cases.

OBJECTIVE AND IMPORTANCE: Although the clinical and histological features of the pathological entity of spinal arachnoiditis ossificans (AO) have been established for some time, less attention has been paid to the treatment. We propose a classification of spinal AO evaluating the possibilities and indications for surgical or conservative treatment. CLINICAL PRESENTATION: Type III has a lumbar localization, presents with less neurological involvement, and usually requires conservative treatment. In Types I and II, which are usually thoracic, clinical worsening justifies surgical decompression or partial removal, whereas total removal is rarely achievable. INTERVENTION: The literature was reviewed, and the reports on three patients were added to the published cases. On the basis of a reappraisal of the computed tomographic and magnetic resonance imaging documentation and the surgical descriptions, the cases of AO were classified into three types: semicircular (Type I), circular (Type II), and englobing the caudal fibers (Type III). The indications for treatment were evaluated in terms of surgical possibilities and outcome. CONCLUSION: The classification proposed on the basis of radiological findings allows sufficient clinical differentiation of AO and evaluation of the possibilities for surgical treatment. The latter is conditioned by the type of arachnoiditis, degree of neurological involvement, and presence of any concomitant pathological findings.

Arachnoiditis↗

Metaplastic ossification in a cutaneous pyogenic granuloma: a case report.

Cutaneous ossification may occur in association with a variety of cutaneous neoplasms and inflammatory conditions, such as pilomatricomas, basal cell carcinomas, nevi, chondroid syringomas, venous stasis, and scars. However, it has rarely been reported in pyogenic granuloma, a relatively common benign vascular tumor of the skin and mucous membranes. We herein presented a rare case of cutaneous pyogenic granuloma with ectopic ossification on the big toe of a 37-year-old man, with high recurrence despite repeated CO2 laser ablations. We propose the hypothesis that vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs) play pathologic roles in the development of ectopic bone formation in pyogenic granuloma.

Adult↗

[Development of the normal infantile hip joints assessed by MRI].

The paper provides an overview of the time of appearance of the secondary ossification centers and closure of the growth plates of the acetabulum and proximal epiphysis of the femur: the triradiate cartilage, the acetabular roof growth cartilage, the subcapital growth cartilage, the growth cartilage of the major trochanter, the growth cartilage of the minor trochanter. The study is based upon 62 MRI scans of healthy hips in 45 patients aged 3-21. The examined hips showed no pathologic traits--neither in the MRI scan nor in X-ray investigation. In Spin Echo and Turbo Spin Echo sequential imaging all obtained slices were used, on GRADIENT ECHO: FISP 3D, FLASH 2D, and FLASH 3D FAT SAT only chosen slices were included in the study. This way the following results were obtained: the ossification center of the major trochanter appears at the age of 3 in girls and at the age of 6 in boys, while the ossification center of the minor trochanter appears at the age of 6 in both sexes. The times of complete ossification of following growth cartilages were observed: for the triradiate cartilage ossification was observed at age 12-15 in girls and 15-16 in boys; for the cartilage of the acetabular roof ossification was noted at age 12-15 in girls and 15-18 in boys; ossification in the subcapital growth cartilage occurred at age 15-17 in girls and 16-18 in boys; the major trochanter growth cartilage ossifies at age 15-16 in girls and 16-18 in boys; for the minor trochanter ossification of the growth cartilage occurs at age 14-16 in girls and at age 16-18 in boys. The secondary ossification center of the pubic bone appears at age 9-11 in girls and 13-16 in boys and the secondary ossification center of the acetabular roof appears at age 13-17 in girls and boys. This study expand our knowledge on the development of the hip joint and facilitate the assessment of hip pathology.

Adolescent↗

Pathologic findings in lung volume reduction surgery.

PURPOSE: Lung volume reduction surgery (LVRS) has re-emerged as an alternative in the management of patients with chronic, debilitating, emphysematous lung disease. This has permitted the formal evaluation of pathologic pulmonary changes present in these patients. This study seeks to describe systematically the pathologic findings present in patients undergoing LVRS. METHODS: Tissue sections stained with hematoxylin-eosin, as well as special stains, were retrospectively reviewed from the specimens of 65 nonconsecutive LVRS patients (male patients, 66%; female patients, 31%; mean age, 63.2+/-6.76 yr). All operations were conducted via an open technique (bilateral, 83%; unilateral, 17%). RESULTS: Histologic emphysema grade was mild in 9%, moderate in 72%, and severe in 19% of patients. Microscopic bullae were noted in 75% of specimens. Three patients, each with radiographic evidence of a lesion preoperatively, had small (1.1 to 2.8 cm) adenocarcinomas. Granulomatous bronchiolitis and pneumonitis were noted in one patient who postoperatively developed progressive respiratory compromise. An old, inactive aspergilloma was found in the specimen of another patient. Additional findings of potential clinical significance included bronchiolitis (54), bronchiolectasis (6), and bronchoalveolar metaplasia (1). Incidental findings included interstitial fibrosis and scar (55), interstitial inflammation (20), calcification (20), and ossification (11), bone marrow emboli (4), chemodectoma (2), and carcinoid tumorlets (1). CONCLUSION: This systematic analysis of the resected specimens from patients undergoing LVRS describes a wide range of pathologic findings, including those clinically relevant, as well as incidental. As the application of LVRS continues to expand, the likelihood of discovering clinically significant pathologic lesions (eg, carcinoma) will undoubtedly increase.

Aged↗

Ossified skeletal muscle hemangioma: radiologic and pathologic features.

Skeletal muscle hemangiomas are relatively uncommon tumors in children and young adults. Although the operative management of these lesions may be affected by their vascularity, the correct preoperative diagnosis is often not made. Ossification of these lesions is rare. Two patients are described whose skeletal muscle hemangiomas contained abundant osseous tissue. This was radiologically reflected by the 'swiss cheese' appearance of the tumors. Such an appearance in an ossified soft tissue mass may allow the correct preoperative diagnosis of this condition.

Adult↗

Pathologic and enzyme histochemical studies on bone formation induced by bone morphogenetic protein in mouse muscle tissue.

Bone morphogenetic protein (BMP) irreversibly induced the differentiation of mesenchymal-type cells into osteoprogenitor cells for endochondral ossification. During the process of BMP-induced differentiation in mice, 4 cell type (chondroblasts, osteoblasts, chondroclasts, and osteoclasts) were examined for phosphatase and succinate dehydrogenase using a wide range of buffers (4.0 less than or equal to pH less than or equal to 9.2). During the chondroid tissue-forming stage (1 week), chondroblast-like or osteoblast-like cells expressed phosphatase activity at 6.8 less than or equal to pH less than or equal to 9.2; chondroclast-like or osteoclast-like cells expressed phosphatase activity at 4.0 less than or equal to pH less than or equal to 5.8. However, mature chondrocytes found in hyaline cartilage expressed phosphatase activity between 6.6 less than or equal to pH less than or equal to 7.6 (2 weeks). During the process of endochondral ossification, alkaline phosphatase activity decreased in osteoblast-like cells with traces of acid phosphatase activity still detectable. Chondroclastic and osteoclastic giant cells were characterized by intense succinate dehydrogenase activity.

Acid Phosphatase↗

Foramen tympanicum, or foramen of Huschke: pathologic cases and anatomic CT study.

BACKGROUND AND PURPOSE: A persistent foramen tympanicum, or foramen of Huschke, is an anatomic variation of the tympanic portion of the temporal bone due to a defect in normal ossification in the first 5 years of life. The foramen is located at the anteroinferior aspect of the external auditory canal (EAC), posteromedial to the temporomandibular joint (TMJ). We sought to define its prevalence, location, and size on high-resolution spiral CT (HRCT). METHODS: We prospectively examined 102 consecutive HRCT studies of the temporal bone (204 ears). HRCT was performed by using 120 kV, 400 mAs, an ultra-high-resolution filter, 0.6-mm section thickness, 0.3-mm section increment, 728 x 728 matrix, and 160-mm field of view. We noted the size and location of the foramen tympanicum relative to the tympanic membrane and calculated its prevalence. Patients with focally decreased tympanic bone thickness of <1 mm at the anteroinferior EAC (between the 3- and 6-o'clock positions) were considered separately. RESULTS: We found a foramen tympanicum was found in six (4.6%) of 130 ears. Mean axial diameter was 4.2 mm, and mean sagittal diameter was 3.6 mm. Focally reduced bone thickness in the same location was found in 45 (35%) ears, with a female preponderance (P = .003). CONCLUSION: HRCT is sensitive for detection of the foramen tympanicum because of its thin sections, high spatial resolution, and multiplanar capabilities. Awareness of this anatomic entity may be useful in evaluating patients with transient otorrhea in whom no otologic cause (e.g., ear infection, TMJ disease) is identified.

Adolescent↗

Progressive osseous heteroplasia, uncommon cause of soft tissue ossification: a case report and review of the literature.

We report a case of an uncommon, recently described disease manifesting shortly after birth, characterized by extensive soft tissue calcification with ossification, progressive osseous heteroplasia. We describe the complex histopathologic patterns present in this case, discuss the main differential diagnoses that the surgical pathologist must consider when confronted by soft tissue ossification, and review the pertinent literature. We conclude that although the morphologic patterns of ossification in progressive osseous heteroplasia are complex and the involvement is extensive, the morphology of the lesions lacks diagnostic specificity. The diagnosis must be based on a consideration of the combined clinical data and radiologic and pathologic findings. This approach alone makes it possible to exclude a number of clinicopathologic entities that manifest with so-called osteoma cutis but whose associated lesions and genetic implications are different.

Calcinosis↗

Osteochondrosis of the primary ossification center of the patella (Köhler's disease of the patella) report of three cases.

Radiography of three boys 5-6 years old with anterior knee pain revealed increased density and irregularity of the patellar ossification centers. A search of the literature suggested that it was osteochondrosis of the primary ossification center of the patella, named after Köhler. Continuing search also revealed that it might be a normal variant instead of an osteochondrosis. A short course of activity modification led to marked improvement in all. The patients were either asymptomatic or experienced minor symptoms 18-34 months after presentation. It was concluded that the process, either physiological or pathological, has a benign course and favorable prognosis.

Child↗