Departamento de Bioquímica y Biologia Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
J Bone Miner Res. 2010 Apr;25(4):912-9. doi: 10.1359/jbmr.091013.
Osteomyelitis (OM) is a bone infection characterized by necrosis and new formation of bone. Because matrix metalloproteases (MMPs) play an important role in bone extracellular matrix remodeling, we investigated the role of some MMP polymorphisms in OM patients. A total of 118 OM patients and 300 blood donors were genotyped for the polymorphisms of MMP1 (-1607 1G/2G) and MMP13 (-77A/G). Levels of MMPs (-1, -2, -3, -8, -9, -10, and -13) and tissue inhibitors of metaloproteases (TIMP-1, -2, and -4) in serum and in human osteoblasts obtained from OM biopsies also were determined. The MMP1 (-1607 2G/2G) genotype was significantly more frequent among OM patients compared with controls [65.3% versus 33.7%, chi(2) = 26.85, odds ratio (OR) = 3.24, 95% confidence interval (CI) 2.03-5.2, p < .0001]. The MMP1 2G allele also was more frequent in OM patients (73.3% versus 57.2%, chi(2) = 37.76, OR = 2.75, 95% CI 1.96-3.85, p < .0001). Carriers of the 2G allele had significantly higher osteoblast MMP1 mRNA and MMP-1 serum levels than noncarriers (p < .04). Interleukin 1alpha (IL-1alpha) increased MMP-1 and -13 protein secretion and Ets1 mRNA expression by OM patients' osteoblasts. No association of the MMP13 (-77 A/G) polymorphism with OM was observed. The MMP1 (-1607 1G/2G) polymorphism might contribute to OM pathogenesis. This could be due to increased expression of MMP-1 by osteoblasts and is regulated by IL-1alpha.
骨髓炎（OM）是一种以骨坏死和新骨形成为特征的骨感染。由于基质金属蛋白酶（MMPs）在骨细胞外基质重塑中发挥重要作用，我们研究了一些 MMP 多态性在 OM 患者中的作用。共对 118 名 OM 患者和 300 名献血者进行了 MMP1（-1607 1G/2G）和 MMP13（-77A/G）多态性的基因分型。还测定了 OM 活检获得的血清和人成骨细胞中 MMPs（-1、-2、-3、-8、-9、-10 和-13）和金属蛋白酶组织抑制剂（TIMP-1、-2 和-4）的水平。与对照组相比，OM 患者的 MMP1（-1607 2G/2G）基因型明显更为常见[65.3%比 33.7%，chi(2) = 26.85，OR = 3.24，95%CI 2.03-5.2，p <.0001]。MMP1 2G 等位基因在 OM 患者中也更为常见（73.3%比 57.2%，chi(2) = 37.76，OR = 2.75，95%CI 1.96-3.85，p <.0001）。MMP1 2G 等位基因携带者的成骨细胞 MMP1 mRNA 和 MMP-1 血清水平明显高于非携带者（p <.04）。白细胞介素 1alpha（IL-1alpha）增加了 OM 患者成骨细胞的 MMP-1 和 -13 蛋白分泌和 Ets1 mRNA 表达。未观察到 MMP13（-77 A/G）多态性与 OM 的相关性。MMP1（-1607 1G/2G）多态性可能导致 OM 的发病机制。这可能是由于成骨细胞中 MMP-1 的表达增加，并且受 IL-1alpha 调节。
