The Experts below are selected from a list of 3480 Experts worldwide ranked by ideXlab platform
Matthew L Warman - One of the best experts on this subject based on the ideXlab platform.
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SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
2016Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous fo
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shp2 regulates chondrocyte terminal differentiation growth plate architecture and skeletal cell fates
PLOS Genetics, 2014Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function mutations, second-hit mutations in PTPN11 can induce Enchondromas by disrupting the organization and delaying the terminal differentiation of growth plate chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells on the bone surface. Furthermore, the data are consistent with paracrine signaling from SHP2-deficient cells causing SHP2-sufficient cells to be incorporated into the lesions.
H T Temple - One of the best experts on this subject based on the ideXlab platform.
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Enchondroma versus chondrosarcoma in the appendicular skeleton differentiating features
Radiographics, 1998Co-Authors: Mark D Murphey, S R Boyea, J A Bojescul, Donald J Flemming, Donald E. Sweet, H T TempleAbstract:Distinction of Enchondroma versus intramedullary chondrosarcoma affecting the appendicular skeleton (proximal to the metacarpals and metatarsals) is a frequent diagnostic dilemma. The authors studied a large series of patients with these lesions (92 with Enchondromas, 95 with chondrosarcomas) using statistical assessment of both clinical parameters and numerous radiologic manifestations on images from multiple modalities to identify differentiating features. Multiple clinical and imaging parameters demonstrated statistically significant differences between Enchondroma and chondrosarcoma, particularly pain related to the lesion, deep endosteal scalloping (greater than two-thirds of cortical thickness), cortical destruction and soft-tissue mass (at computed tomography or magnetic resonance imaging), periosteal reaction (at radiography), and marked uptake of radionuclide (greater than the anterior iliac crest) at bone scintigraphy. All of these features strongly suggested the diagnosis of chondrosarcoma. The...
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Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features.
Radiographics : a review publication of the Radiological Society of North America Inc, 1998Co-Authors: Mark D Murphey, S R Boyea, J A Bojescul, Donald J Flemming, Donald E. Sweet, H T TempleAbstract:Distinction of Enchondroma versus intramedullary chondrosarcoma affecting the appendicular skeleton (proximal to the metacarpals and metatarsals) is a frequent diagnostic dilemma. The authors studied a large series of patients with these lesions (92 with Enchondromas, 95 with chondrosarcomas) using statistical assessment of both clinical parameters and numerous radiologic manifestations on images from multiple modalities to identify differentiating features. Multiple clinical and imaging parameters demonstrated statistically significant differences between Enchondroma and chondrosarcoma, particularly pain related to the lesion, deep endosteal scalloping (greater than two-thirds of cortical thickness), cortical destruction and soft-tissue mass (at computed tomography or magnetic resonance imaging), periosteal reaction (at radiography), and marked uptake of radionuclide (greater than the anterior iliac crest) at bone scintigraphy. All of these features strongly suggested the diagnosis of chondrosarcoma. These criteria allow distinction of appendicular Enchondroma and chondrosarcoma in at least 90% of cases.
Mark D Murphey - One of the best experts on this subject based on the ideXlab platform.
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Differentiating clinical and radiographic features of Enchondroma and secondary chondrosarcoma in the foot
Foot & ankle international, 2006Co-Authors: Donald A. Gajewski, Mark D Murphey, Jeffery B. Burnette, H. Thomas TempleAbstract:Background: Enchondroma is the most common benign tumor of the bones of the foot. Chondrosarcoma in this area is relatively rare with malignant transformation from Enchondroma occurring rarely. In ...
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SOLITARY EPIPHYSEAL EnchondromaS
The Journal of bone and joint surgery. American volume, 2005Co-Authors: Benjamin K. Potter, Brett A. Freedman, Ronald A. Lehman, Scott B. Shawen, Timothy R. Kuklo, Mark D MurpheyAbstract:Background: Enchondromas originating in the epiphyses of long bones are rare. The purpose of the present study was to evaluate the prevalence as well as the radiographic and clinical characteristics of epiphyseal Enchondromas among patients who had been referred to the Armed Forces Institute of Pathology and Walter Reed Army Medical Center. Methods: We performed a retrospective review of 761 patients who had been referred to our two institutions over an approximately fifty-five-year period and who received a final diagnosis of Enchondroma. All lesions had been biopsied, and the pathological diagnosis had been confirmed. Lesions of the hands, feet, or axial skeleton (253 patients) as well as lesions that appeared to originate in the metaphysis or diaphysis (475 patients) were excluded. Only Enchondromas of the long bones that originated in the epiphysis were analyzed. The study group included thirty-three patients (twenty male patients and thirteen female patients) with a mean age of 26.7 years, including eleven patients with open physes. We performed additional descriptive analyses with regard to patient age, gender, lesion location, clinical presentation, and treatment as well as an extensive radiographic analysis. Results: The most common locations were the proximal part of the humerus (ten lesions; 30%) and the distal part of the femur (six lesions; 18%). The most common presenting symptom was pain (twenty-three patients). Radiographic analysis demonstrated extensive matrix mineralization in association with twenty-three lesions. Twenty-eight of the thirty-three lesions were geographically well defined; of these, twenty-one had sclerotic borders, and seven did not. Although all lesions were centered and were predominantly located within the epiphysis, twenty of the thirty-three lesions demonstrated radiographic evidence of metaphyseal extension, including four of the eleven lesions in patients with open physes. Twenty-four lesions extended into the subchondral bone. The mean size of the thirty-three Enchondromas in greatest radiographic dimension was 2.7 cm (range, 1.1 to 4.9 cm). Twenty-six of the thirty-three lesions were amenable to surgical treatment with curettage with or without bone-grafting, with only one recurrence. With the limited follow-up available, no lesion underwent sarcomatous degeneration. Conclusions: Epiphyseal Enchondromas are rare lesions. Although their biologic behavior appears to mirror that of conventional metaphyseal Enchondromas, their proximity to the joint space may lead to more frequent painful symptoms, a propensity for physeal involvement, and the need for earlier definitive surgical intervention. Level of Evidence: Prognostic Level IV. See Instructions to Authors for a complete description of levels of evidence.
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Enchondroma versus chondrosarcoma in the appendicular skeleton differentiating features
Radiographics, 1998Co-Authors: Mark D Murphey, S R Boyea, J A Bojescul, Donald J Flemming, Donald E. Sweet, H T TempleAbstract:Distinction of Enchondroma versus intramedullary chondrosarcoma affecting the appendicular skeleton (proximal to the metacarpals and metatarsals) is a frequent diagnostic dilemma. The authors studied a large series of patients with these lesions (92 with Enchondromas, 95 with chondrosarcomas) using statistical assessment of both clinical parameters and numerous radiologic manifestations on images from multiple modalities to identify differentiating features. Multiple clinical and imaging parameters demonstrated statistically significant differences between Enchondroma and chondrosarcoma, particularly pain related to the lesion, deep endosteal scalloping (greater than two-thirds of cortical thickness), cortical destruction and soft-tissue mass (at computed tomography or magnetic resonance imaging), periosteal reaction (at radiography), and marked uptake of radionuclide (greater than the anterior iliac crest) at bone scintigraphy. All of these features strongly suggested the diagnosis of chondrosarcoma. The...
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Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features.
Radiographics : a review publication of the Radiological Society of North America Inc, 1998Co-Authors: Mark D Murphey, S R Boyea, J A Bojescul, Donald J Flemming, Donald E. Sweet, H T TempleAbstract:Distinction of Enchondroma versus intramedullary chondrosarcoma affecting the appendicular skeleton (proximal to the metacarpals and metatarsals) is a frequent diagnostic dilemma. The authors studied a large series of patients with these lesions (92 with Enchondromas, 95 with chondrosarcomas) using statistical assessment of both clinical parameters and numerous radiologic manifestations on images from multiple modalities to identify differentiating features. Multiple clinical and imaging parameters demonstrated statistically significant differences between Enchondroma and chondrosarcoma, particularly pain related to the lesion, deep endosteal scalloping (greater than two-thirds of cortical thickness), cortical destruction and soft-tissue mass (at computed tomography or magnetic resonance imaging), periosteal reaction (at radiography), and marked uptake of radionuclide (greater than the anterior iliac crest) at bone scintigraphy. All of these features strongly suggested the diagnosis of chondrosarcoma. These criteria allow distinction of appendicular Enchondroma and chondrosarcoma in at least 90% of cases.
Margot E Bowen - One of the best experts on this subject based on the ideXlab platform.
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SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
2016Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous fo
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shp2 regulates chondrocyte terminal differentiation growth plate architecture and skeletal cell fates
PLOS Genetics, 2014Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function mutations, second-hit mutations in PTPN11 can induce Enchondromas by disrupting the organization and delaying the terminal differentiation of growth plate chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells on the bone surface. Furthermore, the data are consistent with paracrine signaling from SHP2-deficient cells causing SHP2-sufficient cells to be incorporated into the lesions.
Wentian Yang - One of the best experts on this subject based on the ideXlab platform.
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SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
2016Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous fo
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shp2 regulates chondrocyte terminal differentiation growth plate architecture and skeletal cell fates
PLOS Genetics, 2014Co-Authors: Margot E Bowen, Ugur M Ayturk, Kyle C Kurek, Wentian Yang, Matthew L WarmanAbstract:Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC) patients causes benign cartilage tumors on the bone surface (exostoses) and within bones (Enchondromas). To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their Enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and Enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function mutations, second-hit mutations in PTPN11 can induce Enchondromas by disrupting the organization and delaying the terminal differentiation of growth plate chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells on the bone surface. Furthermore, the data are consistent with paracrine signaling from SHP2-deficient cells causing SHP2-sufficient cells to be incorporated into the lesions.