Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregul... more Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RA...
Lamin A is a key component of the nuclear lamina produced through post-translational processing o... more Lamin A is a key component of the nuclear lamina produced through post-translational processing of its precursor known as prelamin A.LMNA mutations leading to farnesylated prelamin A accumulation are known to cause lipodystrophy, progeroid and developmental diseases, including Mandibuloacral dysplasia, a mild progeroid syndrome with partial lipodystrophy and altered bone turnover. Thus, degradation of prelamin A is expected to improve the disease phenotype. Here, we show different susceptibilities of prelamin A forms to proteolysis and further demonstrate that treatment with rapamycin efficiently and selectively triggers lysosomal degradation of farnesylated prelamin A, the most toxic processing intermediate. Importantly, rapamycin treatment of Mandibuloacral dysplasia cells, which feature very low levels of the NAD-dependent sirtuin SIRT-1 in the nuclear matrix, restores SIRT-1 localization and distribution of chromatin markers, elicits release of the transcription factor Oct-1 and...
Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal mu... more Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal muscle. Mutations in COL6A genes cause Bethlem Myopathy (BM), Ullrich Congenital Muscular Dystrophy (UCMD) and Myosclerosis Myopathy (MM). Collagen VI deficiency causes increased opening of the mitochondrial permeability transition pore (mPTP), leading to ultrastructural and functional alterations of mitochondria, amplified by impairment of autophagy. Here we report for the first time ultrastructural studies on muscle biopsies from BM and UCMD patients, showing swollen mitochondria with hypodense matrix, disorganized cristae and paracrystalline inclusions, associated with dilated sarcoplasmic reticulum and apoptotic changes. These data were supported by scanning electron microscopy analysis on BM and UCMD cultured cells, showing alterations of the mitochondrial network. Morphometric analysis also revealed a reduced short axis and depicted swelling in about 3% of mitochondria. These data de...
Journal of Bone and Joint Surgery-american Volume, 2006
... Early diagnosis of ceramic liner fracture. Guidelines based on a twelve-year clinical experie... more ... Early diagnosis of ceramic liner fracture. Guidelines based on a twelve-year clinical experience. Toni A, Traina F, Stea S, Sudanese A, Visentin M, Bordini B, Squarzoni S. Laboratorio di Tecnologia Medica--1st Division, Istituti Ortopedici Rizzoli, 40136 Bologna, Italy. ...
Electron microscopy study of muscle biopsies from patients with autosomal-dominant Emery-Dreifuss... more Electron microscopy study of muscle biopsies from patients with autosomal-dominant Emery-Dreifuss muscular dystrophy revealed nuclear alterations in about 10% of the preserved muscle fibers. The major findings consisted of peripheral heterochromatin loss or detachment from the nuclear envelope, and of interchromatin texture alterations. These abnormalities are similar to those reported in an animal model of the disease and to those found in the X-linked form of Emery-Dreifuss muscular dystrophy. These results suggest that an abnormal ultrastructural arrangement of the nuclear periphery is a common feature in the known forms of Emery-Dreifuss muscular dystrophy, and that several proteins of the nuclear scaffold are necessary in muscle cells to maintain the nuclear structural/functional integrity and a normal muscle cell metabolism.
Emery-Dreifuss muscular dystrophy (EMD) is an inherited myopathy characterised by muscle contract... more Emery-Dreifuss muscular dystrophy (EMD) is an inherited myopathy characterised by muscle contractures, progressive muscle wasting and weakness, with humeroperoneal distribution. Cardiac arrhythmia and heart conduction block are also important characteristics of this disease. The X-linked form of EMD is caused by the absence of emerin, encoded by the STA gene (Xq28). Emerin is normally localized in muscle and other tissues at the nuclear rim. Currently, muscle and skin biopsies are used for the immunohistochemical diagnosis. We demonstrate that emerin is present in the cheek oral mucosa, in the exfoliating epithelial cells, and we propose the collection of these cells as a new method for the diagnosis of X-linked EMD patients and the detection of carriers by immunofluorescence techniques: smears from healthy subjects contained about 98% emerin-positive cells, those from X-linked EMD patients contained none and those from carriers contained about 45%. The technique is completely non-invasive, simple, repeatable and inexpensive.
The aim of this study is to localize the α2 laminin chain in normal human skin. The methods used ... more The aim of this study is to localize the α2 laminin chain in normal human skin. The methods used were immuno-gold cytochemistry on cryo-ultramicrotomy sections and thin-section-fracture-label, together with electron microscopy observation. Results were compared with light microscopy peroxidase immuno-staining. Both normal skin samples and skin biopsies from laminin α2 chain deficient congenital muscular dystrophy affected patients were studied. The
Emerin, the protein whose production is altered in the X-linked form of Emery-Dreifuss muscular d... more Emerin, the protein whose production is altered in the X-linked form of Emery-Dreifuss muscular distrophy, has been hypothesized to be associated with the nuclear matrix on the basis of biochemical studies. In addition, immunocytochemical data reported its localization at the nuclear periphery, on the nuclear lamina, in sections of several normal tissues. We investigated the association of emerin with the nuclear matrix, by using cultured cells (SaOS-2, MG63 and HeLa-S3) and their in situ extracted matrix as a model, and immunocytochemical methods, both at the light and electron microscope level. Our results show a normal presence of emerin in the cultured cells and the specific persistence of emerin on the lamina of the in situ extracted nuclear matrix. This suggests a tight binding between emerin and the nuclear lamina independently from the interactions between the C-terminal hydrophobic domain of the protein and the inner nuclear membrane.
Bethlem myopathy is a well-defined clinical entity among collagen VI disorders, featuring proxima... more Bethlem myopathy is a well-defined clinical entity among collagen VI disorders, featuring proximal muscle weakness and contractures of the fingers, wrists, and ankles. It is an early-onset, slowly progressive, and relatively mild disease, invariably associated to date with heterozygous dominant mutations in the 3 collagen VI genes. We have characterized the clinical, laboratory, and genetic features of autosomal recessive Bethlem myopathy in 2 unrelated patients. This study is based on clinical, histochemical, immunocytochemical, and electron microscope evaluation of the muscle and dermal fibroblasts, CT imaging of the muscles, and biochemical and molecular analysis. Both patients carry a truncating COL6A2 mutation (Q819X; R366X) associated with missense changes in the partnering allele lying within the C2 domain of the alpha2(VI) chain (D871N; R843W-R830Q). They show decreased amounts of collagen VI in the basal lamina of muscle fibers and in dermal fibroblast cultures and altered behavior of collagen VI tetramers. Biochemical studies supported the pathogenic effect of identified amino acid substitutions, which involve strictly conserved residues. The reported patients illustrate the occurrence of Bethlem myopathy with a recessive mode of inheritance. This observation completes the hereditary pattern in collagen VI myopathies with both Ullrich congenital muscular dystrophy and Bethlem myopathy underlined by either recessive or dominant effecting mutations. This finding has relevant implications for genetic counseling and molecular characterization of patients with Bethlem myopathy, as well as for genotype-phenotype correlations in collagen VI disorders.
To determine the clinical and molecular features of a new phenotype related to collagen VI myopat... more To determine the clinical and molecular features of a new phenotype related to collagen VI myopathies. We examined two patients belonging to a consanguineous family affected by myosclerosis myopathy, screened for mutations of collagen VI genes, and performed a detailed biochemical and morphologic analysis of the muscle biopsy and cultured fibroblasts. The patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. The truncated chain associated with the other two chains, giving rise to secreted collagen VI. Monomers containing the truncated chain were assembled into dimers, but tetramers were almost absent; secreted collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts. Mutated collagen did not correctly localize in the basement membrane of muscle fibers and was absent in the capillary wall. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, and increased number of pericytes. This familial case has the characteristic features of myosclerosis myopathy and carries a homozygous COL6A2 mutation responsible for a peculiar pattern of collagen VI defects. Our study demonstrates that myosclerosis myopathy should be considered a collagen VI disorder allelic to Ullrich congenital muscular dystrophy and Bethlem myopathy.
Ultrastructural alterations in the nuclear architecture were found in skeletal muscle and skin cu... more Ultrastructural alterations in the nuclear architecture were found in skeletal muscle and skin cultured cells from a patient affected by X-linked Emery-Dreifuss muscular dystrophy (EMD) carrying a null mutation. The molecular defect of X-linked EMD is the absence of emerin, a nuclear envelope-associated protein which is considered a component of the nuclear lamina. The nuclear changes were present in skeletal muscle and skin cultured cells with a frequency of about 10% and 18%, respectively. The main structures of the nuclear periphery were involved: lamina and nuclear envelope-associated heterochromatin were affected, whereas the cisterna and the pore complexes appeared preserved, and the cytoplasm of the same cells appeared normal. Analogous localized defects were detectable by immunolabeling with antilamin A/C and B2 antibodies, as well as by selective propidium iodide chromatin staining. The lesions we describe could be the result of anomalous nuclear lamina organization in the absence of emerin.
Fibronectin is one of the main components of the extracellular matrix and associates with a varie... more Fibronectin is one of the main components of the extracellular matrix and associates with a variety of other matrix molecules including collagens. We demonstrate that the absence of secreted type VI collagen in cultured primary fibroblasts affects the arrangement of fibronectin in the extracellular matrix. We observed a fine network of collagen VI filaments and fibronectin fibrils in the extracellular matrix of normal murine and human fibroblasts. The two microfibrillar systems did not colocalize, but were interconnected at some discrete sites which could be revealed by immunoelectron microscopy. Direct interaction between collagen VI and fibronectin was also demonstrated by far western assay. When primary fibroblasts from Col6a1 null mutant mice were cultured, collagen VI was not detected in the extracellular matrix and a different pattern of fibronectin organization was observed, with fibrils running parallel to the long axis of the cells. Similarly, an abnormal fibronectin deposition was observed in fibroblasts from a patient affected by Bethlem myopathy, where collagen VI secretion was drastically reduced. The same pattern was also observed in normal fibroblasts after in vivo perturbation of collagen VI-fibronectin interaction with the 3C4 anti-collagen VI monoclonal antibody. Competition experiments with soluble peptides indicated that the organization of fibronectin in the extracellular matrix was impaired by added soluble collagen VI, but not by its triple helical (pepsin-resistant) fragments. These results indicate that collagen VI mediates the three-dimensional organization of fibronectin in the extracellular matrix of cultured fibroblasts.
The first clinical sign of ceramic hip prosthesis failure is hip noise. We therefore investigated... more The first clinical sign of ceramic hip prosthesis failure is hip noise. We therefore investigated whether isolation, observation at scanning electron microscopy, and chemical identification with microanalysis of particles from synovial fluid of "noisy hip" could be predictive of ceramic damage. Firstly, the level of "physiological wear" of well functioning ceramic-on-ceramic hip prostheses was assessed with this method, then the test was validated as diagnostic method for liner fracture. Twelve asymptomatic patients were enrolled to demonstrate the first aim; 39 cases of noisy hip (GROUP 1), and 7 cases of pending failure not related to ceramic (GROUP 2) were enrolled for the second aim. The analysis of the synovial fluid of the 12 asymptomatic patients allowed to set the "physiological wear" threshold. The analysis of GROUP 1 hips demonstrated the presence of ceramic particles (2 physiological, 12 mild, and 25 strong). The analysis of GROUP 2 showed a physiological presence of ceramic particles in all cases. Revision surgery in GROUP 1 was performed in 16 hips out 25 with strong ceramic particle presence and 2 out of 12 with mild ceramic particle presence. Failure of the ceramic component was evident in all but one of these cases, while the integrity of components was demonstrated in all seven hips of GROUP 2. Synovial fluid microanalysis can be a useful surrogate in predicting ceramic failure particularly when a strong presence of ceramic particles is observed. On the contrary there is not enough evidence to predict ceramic failure in presence of mild positivity.
Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregul... more Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RA...
Lamin A is a key component of the nuclear lamina produced through post-translational processing o... more Lamin A is a key component of the nuclear lamina produced through post-translational processing of its precursor known as prelamin A.LMNA mutations leading to farnesylated prelamin A accumulation are known to cause lipodystrophy, progeroid and developmental diseases, including Mandibuloacral dysplasia, a mild progeroid syndrome with partial lipodystrophy and altered bone turnover. Thus, degradation of prelamin A is expected to improve the disease phenotype. Here, we show different susceptibilities of prelamin A forms to proteolysis and further demonstrate that treatment with rapamycin efficiently and selectively triggers lysosomal degradation of farnesylated prelamin A, the most toxic processing intermediate. Importantly, rapamycin treatment of Mandibuloacral dysplasia cells, which feature very low levels of the NAD-dependent sirtuin SIRT-1 in the nuclear matrix, restores SIRT-1 localization and distribution of chromatin markers, elicits release of the transcription factor Oct-1 and...
Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal mu... more Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal muscle. Mutations in COL6A genes cause Bethlem Myopathy (BM), Ullrich Congenital Muscular Dystrophy (UCMD) and Myosclerosis Myopathy (MM). Collagen VI deficiency causes increased opening of the mitochondrial permeability transition pore (mPTP), leading to ultrastructural and functional alterations of mitochondria, amplified by impairment of autophagy. Here we report for the first time ultrastructural studies on muscle biopsies from BM and UCMD patients, showing swollen mitochondria with hypodense matrix, disorganized cristae and paracrystalline inclusions, associated with dilated sarcoplasmic reticulum and apoptotic changes. These data were supported by scanning electron microscopy analysis on BM and UCMD cultured cells, showing alterations of the mitochondrial network. Morphometric analysis also revealed a reduced short axis and depicted swelling in about 3% of mitochondria. These data de...
Journal of Bone and Joint Surgery-american Volume, 2006
... Early diagnosis of ceramic liner fracture. Guidelines based on a twelve-year clinical experie... more ... Early diagnosis of ceramic liner fracture. Guidelines based on a twelve-year clinical experience. Toni A, Traina F, Stea S, Sudanese A, Visentin M, Bordini B, Squarzoni S. Laboratorio di Tecnologia Medica--1st Division, Istituti Ortopedici Rizzoli, 40136 Bologna, Italy. ...
Electron microscopy study of muscle biopsies from patients with autosomal-dominant Emery-Dreifuss... more Electron microscopy study of muscle biopsies from patients with autosomal-dominant Emery-Dreifuss muscular dystrophy revealed nuclear alterations in about 10% of the preserved muscle fibers. The major findings consisted of peripheral heterochromatin loss or detachment from the nuclear envelope, and of interchromatin texture alterations. These abnormalities are similar to those reported in an animal model of the disease and to those found in the X-linked form of Emery-Dreifuss muscular dystrophy. These results suggest that an abnormal ultrastructural arrangement of the nuclear periphery is a common feature in the known forms of Emery-Dreifuss muscular dystrophy, and that several proteins of the nuclear scaffold are necessary in muscle cells to maintain the nuclear structural/functional integrity and a normal muscle cell metabolism.
Emery-Dreifuss muscular dystrophy (EMD) is an inherited myopathy characterised by muscle contract... more Emery-Dreifuss muscular dystrophy (EMD) is an inherited myopathy characterised by muscle contractures, progressive muscle wasting and weakness, with humeroperoneal distribution. Cardiac arrhythmia and heart conduction block are also important characteristics of this disease. The X-linked form of EMD is caused by the absence of emerin, encoded by the STA gene (Xq28). Emerin is normally localized in muscle and other tissues at the nuclear rim. Currently, muscle and skin biopsies are used for the immunohistochemical diagnosis. We demonstrate that emerin is present in the cheek oral mucosa, in the exfoliating epithelial cells, and we propose the collection of these cells as a new method for the diagnosis of X-linked EMD patients and the detection of carriers by immunofluorescence techniques: smears from healthy subjects contained about 98% emerin-positive cells, those from X-linked EMD patients contained none and those from carriers contained about 45%. The technique is completely non-invasive, simple, repeatable and inexpensive.
The aim of this study is to localize the α2 laminin chain in normal human skin. The methods used ... more The aim of this study is to localize the α2 laminin chain in normal human skin. The methods used were immuno-gold cytochemistry on cryo-ultramicrotomy sections and thin-section-fracture-label, together with electron microscopy observation. Results were compared with light microscopy peroxidase immuno-staining. Both normal skin samples and skin biopsies from laminin α2 chain deficient congenital muscular dystrophy affected patients were studied. The
Emerin, the protein whose production is altered in the X-linked form of Emery-Dreifuss muscular d... more Emerin, the protein whose production is altered in the X-linked form of Emery-Dreifuss muscular distrophy, has been hypothesized to be associated with the nuclear matrix on the basis of biochemical studies. In addition, immunocytochemical data reported its localization at the nuclear periphery, on the nuclear lamina, in sections of several normal tissues. We investigated the association of emerin with the nuclear matrix, by using cultured cells (SaOS-2, MG63 and HeLa-S3) and their in situ extracted matrix as a model, and immunocytochemical methods, both at the light and electron microscope level. Our results show a normal presence of emerin in the cultured cells and the specific persistence of emerin on the lamina of the in situ extracted nuclear matrix. This suggests a tight binding between emerin and the nuclear lamina independently from the interactions between the C-terminal hydrophobic domain of the protein and the inner nuclear membrane.
Bethlem myopathy is a well-defined clinical entity among collagen VI disorders, featuring proxima... more Bethlem myopathy is a well-defined clinical entity among collagen VI disorders, featuring proximal muscle weakness and contractures of the fingers, wrists, and ankles. It is an early-onset, slowly progressive, and relatively mild disease, invariably associated to date with heterozygous dominant mutations in the 3 collagen VI genes. We have characterized the clinical, laboratory, and genetic features of autosomal recessive Bethlem myopathy in 2 unrelated patients. This study is based on clinical, histochemical, immunocytochemical, and electron microscope evaluation of the muscle and dermal fibroblasts, CT imaging of the muscles, and biochemical and molecular analysis. Both patients carry a truncating COL6A2 mutation (Q819X; R366X) associated with missense changes in the partnering allele lying within the C2 domain of the alpha2(VI) chain (D871N; R843W-R830Q). They show decreased amounts of collagen VI in the basal lamina of muscle fibers and in dermal fibroblast cultures and altered behavior of collagen VI tetramers. Biochemical studies supported the pathogenic effect of identified amino acid substitutions, which involve strictly conserved residues. The reported patients illustrate the occurrence of Bethlem myopathy with a recessive mode of inheritance. This observation completes the hereditary pattern in collagen VI myopathies with both Ullrich congenital muscular dystrophy and Bethlem myopathy underlined by either recessive or dominant effecting mutations. This finding has relevant implications for genetic counseling and molecular characterization of patients with Bethlem myopathy, as well as for genotype-phenotype correlations in collagen VI disorders.
To determine the clinical and molecular features of a new phenotype related to collagen VI myopat... more To determine the clinical and molecular features of a new phenotype related to collagen VI myopathies. We examined two patients belonging to a consanguineous family affected by myosclerosis myopathy, screened for mutations of collagen VI genes, and performed a detailed biochemical and morphologic analysis of the muscle biopsy and cultured fibroblasts. The patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. The truncated chain associated with the other two chains, giving rise to secreted collagen VI. Monomers containing the truncated chain were assembled into dimers, but tetramers were almost absent; secreted collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts. Mutated collagen did not correctly localize in the basement membrane of muscle fibers and was absent in the capillary wall. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, and increased number of pericytes. This familial case has the characteristic features of myosclerosis myopathy and carries a homozygous COL6A2 mutation responsible for a peculiar pattern of collagen VI defects. Our study demonstrates that myosclerosis myopathy should be considered a collagen VI disorder allelic to Ullrich congenital muscular dystrophy and Bethlem myopathy.
Ultrastructural alterations in the nuclear architecture were found in skeletal muscle and skin cu... more Ultrastructural alterations in the nuclear architecture were found in skeletal muscle and skin cultured cells from a patient affected by X-linked Emery-Dreifuss muscular dystrophy (EMD) carrying a null mutation. The molecular defect of X-linked EMD is the absence of emerin, a nuclear envelope-associated protein which is considered a component of the nuclear lamina. The nuclear changes were present in skeletal muscle and skin cultured cells with a frequency of about 10% and 18%, respectively. The main structures of the nuclear periphery were involved: lamina and nuclear envelope-associated heterochromatin were affected, whereas the cisterna and the pore complexes appeared preserved, and the cytoplasm of the same cells appeared normal. Analogous localized defects were detectable by immunolabeling with antilamin A/C and B2 antibodies, as well as by selective propidium iodide chromatin staining. The lesions we describe could be the result of anomalous nuclear lamina organization in the absence of emerin.
Fibronectin is one of the main components of the extracellular matrix and associates with a varie... more Fibronectin is one of the main components of the extracellular matrix and associates with a variety of other matrix molecules including collagens. We demonstrate that the absence of secreted type VI collagen in cultured primary fibroblasts affects the arrangement of fibronectin in the extracellular matrix. We observed a fine network of collagen VI filaments and fibronectin fibrils in the extracellular matrix of normal murine and human fibroblasts. The two microfibrillar systems did not colocalize, but were interconnected at some discrete sites which could be revealed by immunoelectron microscopy. Direct interaction between collagen VI and fibronectin was also demonstrated by far western assay. When primary fibroblasts from Col6a1 null mutant mice were cultured, collagen VI was not detected in the extracellular matrix and a different pattern of fibronectin organization was observed, with fibrils running parallel to the long axis of the cells. Similarly, an abnormal fibronectin deposition was observed in fibroblasts from a patient affected by Bethlem myopathy, where collagen VI secretion was drastically reduced. The same pattern was also observed in normal fibroblasts after in vivo perturbation of collagen VI-fibronectin interaction with the 3C4 anti-collagen VI monoclonal antibody. Competition experiments with soluble peptides indicated that the organization of fibronectin in the extracellular matrix was impaired by added soluble collagen VI, but not by its triple helical (pepsin-resistant) fragments. These results indicate that collagen VI mediates the three-dimensional organization of fibronectin in the extracellular matrix of cultured fibroblasts.
The first clinical sign of ceramic hip prosthesis failure is hip noise. We therefore investigated... more The first clinical sign of ceramic hip prosthesis failure is hip noise. We therefore investigated whether isolation, observation at scanning electron microscopy, and chemical identification with microanalysis of particles from synovial fluid of "noisy hip" could be predictive of ceramic damage. Firstly, the level of "physiological wear" of well functioning ceramic-on-ceramic hip prostheses was assessed with this method, then the test was validated as diagnostic method for liner fracture. Twelve asymptomatic patients were enrolled to demonstrate the first aim; 39 cases of noisy hip (GROUP 1), and 7 cases of pending failure not related to ceramic (GROUP 2) were enrolled for the second aim. The analysis of the synovial fluid of the 12 asymptomatic patients allowed to set the "physiological wear" threshold. The analysis of GROUP 1 hips demonstrated the presence of ceramic particles (2 physiological, 12 mild, and 25 strong). The analysis of GROUP 2 showed a physiological presence of ceramic particles in all cases. Revision surgery in GROUP 1 was performed in 16 hips out 25 with strong ceramic particle presence and 2 out of 12 with mild ceramic particle presence. Failure of the ceramic component was evident in all but one of these cases, while the integrity of components was demonstrated in all seven hips of GROUP 2. Synovial fluid microanalysis can be a useful surrogate in predicting ceramic failure particularly when a strong presence of ceramic particles is observed. On the contrary there is not enough evidence to predict ceramic failure in presence of mild positivity.
Uploads
Papers