Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome

被引:14
作者
Lombardi, F. [1 ]
Fasciglione, G. F. [2 ]
D'Apice, M. R. [1 ]
Vielle, A. [1 ]
D'Adamo, M. [3 ]
Sbraccia, P. [3 ]
Marini, S. [2 ]
Borgiani, P. [1 ]
Coletta, M. [2 ]
Novelli, G. [1 ,4 ]
机构
[1] Univ Roma Tor Vergata, Dept Biopathol & Diagnost Imaging, I-00133 Rome, Italy
[2] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
[3] Univ Roma Tor Vergata, Dept Internal Med, I-00133 Rome, Italy
[4] Univ Arkansas Med Sci, Dept Cardiovasc Med, Little Rock, AR 72205 USA
关键词
bone remodelling; laminopathies; mandibuloacral dysplasia; MMPs;
D O I
10.1111/j.1399-0004.2008.01034.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n = 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL-1 beta were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.
引用
收藏
页码:374 / 383
页数:10
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