Hopwood B, Tsykin A, Findlay D M, Fazzalari N L
Division of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
Bone. 2009 Jan;44(1):87-101. doi: 10.1016/j.bone.2008.08.120. Epub 2008 Sep 10.
Osteoporosis (OP) is a common age-related systemic skeletal disease, with a strong genetic component, characterised by loss of bone mass and strength, which leads to increased bone fragility and susceptibility to fracture. Although some progress has been made in identifying genes that may contribute to OP disease, much of the genetic component of OP has yet to be accounted for. Therefore, to investigate the molecular basis for the changes in bone causally involved in OP and fragility fracture, we have used a microarray approach. We have analysed altered gene expression in human OP fracture bone by comparing mRNA in bone from individuals with fracture of the neck of the proximal femur (OP) with that from age-matched individuals with osteoarthritis (OA), and control (CTL) individuals with no known bone pathology. The OA sample set was included because an inverse association, with respect to bone density, has been reported between OA and the OP individuals. Compugen H19K oligo human microarray slides were used to compare the gene expression profiles of three sets of female samples comprising, 10 OP-CTL, 10 OP-OA, and 10 OA-CTL sample pairs. Using linear models for microarray analysis (Limma), 150 differentially expressed genes in OP bone with t scores >5 were identified. Differential expression of 32 genes in OP bone was confirmed by real time PCR analysis (p<0.01). Many of the genes identified have known or suspected roles in bone metabolism and in some cases have been implicated previously in OP pathogenesis. Three major sets of differentially expressed genes in OP bone were identified with known or suspected roles in either osteoblast maturation (PRRX1, ANXA2, ST14, CTSB, SPARC, FST, LGALS1, SPP1, ADM, and COL4A1), myelomonocytic differentiation and osteoclastogenesis (TREM2, ANXA2, IL10, CD14, CCR1, ADAM9, CCL2, CTGF, and KLF10), or adipogenesis, lipid and/or glucose metabolism (IL10, MARCO, CD14, AEBP1, FST, CCL2, CTGF, SLC14A1, ANGPTL4, ADM, TAZ, PEA15, and DOK4). Altered expression of these genes and others in these groups is consistent with previously suggested underlying molecular mechanisms for OP that include altered osteoblast and osteoclast differentiation and function, and an imbalance between osteoblastogenesis and adipogenesis.
骨质疏松症（OP）是一种常见的与年龄相关的全身性骨骼疾病，具有很强的遗传成分，其特征是骨量和骨强度丧失，导致骨脆性增加和易发生骨折。尽管在确定可能导致OP疾病的基因方面已经取得了一些进展，但OP的许多遗传成分仍有待解释。因此，为了研究OP和脆性骨折中骨变化的分子基础，我们采用了微阵列方法。我们通过比较股骨近端颈骨折患者（OP）的骨组织mRNA与年龄匹配的骨关节炎（OA）患者以及无已知骨病理的对照（CTL）个体的骨组织mRNA，分析了人类OP骨折骨中基因表达的改变。纳入OA样本组是因为据报道OA与OP个体之间在骨密度方面存在负相关。使用Compugen H19K寡核苷酸人类微阵列载玻片比较了三组女性样本的基因表达谱，每组包括10对OP-CTL、10对OP-OA和10对OA-CTL样本。使用微阵列分析的线性模型（Limma），鉴定出OP骨中150个差异表达基因，其t值>5。通过实时PCR分析证实了OP骨中32个基因的差异表达（p<0.01）。许多鉴定出的基因在骨代谢中具有已知或疑似作用，在某些情况下，先前已涉及OP的发病机制。在OP骨中鉴定出三组主要的差异表达基因，它们在成骨细胞成熟（PRRX1、ANXA2、ST14、CTSB、SPARC、FST、LGALS1、SPP1、ADM和COL4A1）、骨髓单核细胞分化和破骨细胞生成（TREM2、ANXA2、IL10、CD14、CCR1、ADAM9、CCL2、CTGF和KLF10）或脂肪生成、脂质和/或葡萄糖代谢（IL10、MARCO、CD14、AEBP1、FST、CCL2、CTGF、SLC14A1、ANGPTL4、ADM、TAZ、PEA15和DOK4）中具有已知或疑似作用。这些基因和其他组中基因表达的改变与先前提出的OP潜在分子机制一致，包括成骨细胞和破骨细胞分化及功能的改变，以及成骨细胞生成与脂肪生成之间的失衡。
