Radiological findings in NAO syndrome

Al-Otaibi, Leftan; Al‐Mayouf, Sulaiman M.; Majeed, Mahmoud; Al-Eid, Wea'am; Bahabri, Sultan; Hugosson, Claes

doi:10.1007/s00247-001-0649-4

Cited by 11 publications

(6 citation statements)

References 13 publications

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“…Gender effects were not observed in the knock-out mice, nor are they reported in NAO patients. Arthropathy, characteristic of human NAO syndrome (12)(13)(14), was not observed in Mmp2 Ϫ/Ϫ mice at any age (data not shown). The Mmp2 Ϫ/Ϫ mice, however, are more susceptible to antibody-induced arthritis (21), suggesting that some additional factors, environmental or genetic, could be involved in the pathogenesis of arthritis in human NAO syndrome.…”

Section: ϫ/ϫ Mice Have Facial Abnormalities and Other Bone Alterationmentioning

confidence: 86%

“…Recent linkage analysis suggests that a loss of function mutation of MMP2 causes a human autosomal recessive disorder with multicentric nodulosis, arthropathy with joint erosion, and osteolysis, termed NAO syndrome (10,11). This syndrome also includes facial abnormalities and generalized osteoporosis (12)(13)(14). The finding that NAO syndrome is caused by a loss of MMP-2 activity raises questions about how an ECMdegrading enzyme affects bone volume (10,11).…”

Section: Variae Successful Transplantation Of Wild-type Periosteum Rmentioning

confidence: 99%

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A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

Inoue

Mikuni-Takagaki

Oikawa

et al. 2006

Journal of Biological Chemistry

180

171

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Bone is continuously remodeled to adopt a volume appropriate for the local environment; the amount of bone deposited depends on the balance between bone formation and resorption by bone cells, osteoblasts, osteoclasts, and osteocytes (1). Osteoblasts are bone-forming cells that differentiate from mesenchymal stem cells and secrete extracellular matrix (ECM) 4 proteins, which are subsequently mineralized. Osteoclasts are bone-resorbing cells that differentiate from hematopoietic stem cells and degrade bone ECM proteins after demineralization in the extracellular space (Howship's lacunae) adjacent to the ruffled borders. In contrast to osteoblasts and osteoclasts, which act at bone surfaces, osteocytes, cells of osteoblastic lineage, are embedded in bone and are terminally differentiated. Osteocytes extend their dendritic processes into the bone matrix to constitute a well developed canalicular network with other cells. Although osteocytes are the most abundant cell type in bone tissue, their role in bone metabolism is not firmly established.ECM production and degradation by bone cells are critical steps in bone metabolism (1), and disturbed ECM turnover leads to bone disease. Type I collagen is a major ECM component. Secreted type I collagen molecules are processed by propeptidases and cross-linked by lysyl oxidases into mature collagen. Mutations of genes encoding type I collagen cause the bone disease osteogenesis imperfecta (2). Type I collagens are mainly degraded by matrix metalloproteinases (MMPs), which exert their enzymatic activity at a neutral pH in a zinc ion-dependent manner (3, 4). Several MMPs are expressed in bone tissue (5-9). MMPs may play a role in osteoclastic bone resorption (4, 5). Osteoblasts and osteocytes also produce MMPs such as MMP-2 and MMP-13 (7-9). Recent linkage analysis suggests that a loss of function mutation of MMP2 causes a human autosomal recessive disorder with multicentric nodulosis, arthropathy with joint erosion, and osteolysis, termed NAO syndrome (10, 11). This syndrome also includes facial abnormalities and generalized * This work was supported in part by a grant from the Ministry for Welfare and Health of Japan (to S. I.), by a Sasagawa Scientific Research Grant from the Japan Science Society (to K. I.), by a grant from the Japan Space Forum, National Space Development Agency of Japan (NASDA) (to N. M.), and by a research grant from the National Institutes of Health (to S. M. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 4 The abbreviations used are: ECM, extracellular matrix; DMP-1, dentin matrix protein 1; DMEM, Dulbecco's modified Eagle's medium; MMP, matrix metalloproteinase; NAO, nodulosis, arthropathy, and osteolysis; BMD, bone mineral density; pQCT, peripheral quantitative computed tomography; MAR, mineral apposition rate; BFR/BS, ratio of bone formation rate to bone surface.

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Section: ϫ/ϫ Mice Have Facial Abnormalities and Other Bone Alterationmentioning

confidence: 86%

Section: Variae Successful Transplantation Of Wild-type Periosteum Rmentioning

confidence: 99%

A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

Inoue

Mikuni-Takagaki

Oikawa

et al. 2006

Journal of Biological Chemistry

180

171

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“…MMP‐2 in its active form (62 kDa) is the most important MMP in preserving bone mass. Recent evidences have demonstrated that a deficiency of MMP‐2 induces a bone disorder characterized by the destruction of bone tissue in the form of nodules, arthritis and osteolysis (NAO syndrome), which also includes generalized osteoporosis (Al‐Otaibi et al, 2002; Inoue et al, 2006), an occurrence that suggests a more complex role of this gelatinase in the development and maintenance of bone (Mosig et al, 2007). Ovariectomy reduces the activity and expression of MMP‐2 and also the expression of type I and III collagen (Zecchin et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects of resistance training on matrix metalloproteinase‐2 activity and biomechanical and physical properties of bone in ovariectomized and intact rats

Shiguemoto

Prestes

Leite

et al. 2011

Scandinavian Med Sci Sports

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The purpose of this study was to investigate the influence of resistance training on the activity of matrix metalloproteinase (MMP)-2 and bone biomechanical properties in ovariectomized and intact rats. Forty-eight female rats were divided into two distinct groups, ovariectomized (OVX) and intact (Int), which were subdivided into three similar subgroups: sedentary, acute exercise and chronic exercise. Rats performed a resistance training for 12 weeks in which animals climbed a vertical ladder of 1.1 m with weights attached to their tails. Sessions were performed with an interval of 3, 4-9 and 8-12 days scaled dynamic movements of climbing. Biomechanical and physical analyses were performed using a universal testing machine, and MMP-2 activity analysis by zymography. Bone density (BD), mineral density (MD), maximum load and fracture load was reduced in sedentary and acute exercise OVX groups compared with the sedentary intact group (P<0.05); in contrast, chronically trained groups (OVX and Int) showed a significant increase in BD, MD and fracture load compared with all the other groups. MMP-2 activity in chronically trained groups also showed a significant increase, while the sedentary OVX group showed a decrease in MMP-2 activity compared with the intact sedentary group (P<0.05). Our results suggest that the resistance training proposed in our work was efficient in reverting the deleterious effects of ovariectomy on bone tissue, and also produced modeling effects in intact rats. On the other hand, ovariectomy reduced the activity of MMP-2 and produced deleterious effects on bone tissue, mimicking menopause intrinsically.

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“…However, these features are not always present and have occasionally been observed in other osteolysis syndromes. NAO, the most recently created entity, is characterized by moderate‐to‐severe osteolysis and particularly prominent and painful subcutaneous nodules (8–10). The ISDS nosology considers NAO a variant of Torg syndrome, while Winchester syndrome is classified as a separate disease (2).…”

Section: Classification Of Osteolyses As Proposed By the 2001 Nosologmentioning

confidence: 99%

Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2

et al. 2005

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The inherited osteolysis syndromes are a heterogeneous group of skeletal disorders whose classification is still uncertain. Three osteolysis syndromes show autosomal recessive inheritance and multicentric involvement: Torg syndrome (OMIM 259600), Winchester syndrome (OMIM 277950) and Nodulosis-Arthropathy-Osteolysis syndrome (NAO; OMIM 605156). The 2001 Nosology of the International Skeletal Dysplasia Society (Hall CM, Am J Med Genet 2002: 113: 65) classifies NAO as a variant of Torg syndrome, while Winchester syndrome is considered as a separate disorder. Recently, mutations in the matrix metalloproteinase 2 (MMP2) gene were identified in affected individuals with a clinical diagnosis of NAO in two Arab families. We report a homozygous missense mutation (E404K) in the active site of MMP2 in a 21-year-old woman with a severe form of osteolysis best compatible with a diagnosis of Winchester syndrome. The clinical and molecular findings suggest that Torg, NAO and Winchester syndromes are allelic disorders that form a clinical spectrum.

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Radiological findings in NAO syndrome

Abstract: Our study is the first report of the detailed radiological findings of NAO syndrome. In NAO syndrome, both the axial and appendicular skeleton are involved

Cited by 11 publications

References 13 publications

A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

Effects of resistance training on matrix metalloproteinase‐2 activity and biomechanical and physical properties of bone in ovariectomized and intact rats

Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2

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