Identification of differentially expressed genes between osteoarthritic and normal trabecular bone from the intertrochanteric region of the proximal femur using cDNA microarray analysis

Hopwood, Blair; Gronthos, Stan; Kuliwaba, J.S.; Robey, Pamela Gehron; Findlay, David M.; Fazzalari, N.L.

doi:10.1016/j.bone.2005.02.003

Cited by 21 publications

(18 citation statements)

References 56 publications

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“…These differences in the results may be due to the fact that the studies were carried out at different moments in osteoblastic maturation with changes in the VDR expression [24]. As we analyzed cultures when they had reached cellular confluence, in both groups, the differences we found must be due to true differences between both diseases [22,23,32].…”

Section: Discussioncontrasting

confidence: 53%

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis

Giner

Rios

Montoya

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussioncontrasting

confidence: 53%

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis

Giner

Rios

Montoya

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…Candidate genes were selected from previous microarray reports (Pacicca et al, 2003;Wieczorek et al, 2003;Salim et al, 2004;Tardif et al, 2004;Fang et al, 2005;Hopwood et al, 2005;Zhou et al, 2005). SNPs in these genes were selected based on a call rate (CR) ＞ 0.90, minor allele frequency (MAF) ＞ 0.05, and Hardy-Weinberg equilibrium (HWE) ＞ 0.05 using a public database (http://www.ncbi.nlm.nih.gov/SNP/).…”

Section: Resultsmentioning

confidence: 99%

“…Normal and human mesenchymal stem cells (hMSC) were prepared from femoral tissue from osteoarthritis, osteoarthritic human chondrocytes, and the femur fracture in rat. Human and mouse bone marrow-derived MSCs from normoxic and hypoxic conditions were also used (Pacicca et al, 2003;Wieczorek et al, 2003;Salim et al, 2004;Tardif et al, 2004;Fang et al, 2005;Hopwood et al, 2005;Zhou et al, 2005).…”

Section: Candidate Gene and Snp Selectionmentioning

confidence: 99%

Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head

Hong

Kim

et al. 2010

Exp Mol Med

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Abbreviations: HWE, Hardy-Weinberg equilibrium; LD, linkage disequilibrium; MAF, minor allele frequency; ONFH, osteonecrosis of the femoral head; SNP, single nucleotide polymorphism AbstractMultiple factors have been implicated in the development of osteonecrosis of the femoral head (ONFH). In particular, non-traumatic ONFH is directly or indirectly related to injury of the vascular supply to the femoral head. Thus, hypoxia in the femoral head caused by impaired blood flow may be an important risk factor for ONFH. In this study, we investigated whether genetic variations of angiogenesis-and hypoxia-related genes contribute to an increased risk for the development of ONFH. Candidate genes were selected based on known hypoxia and angiogenesis pathways. An association study was performed using an Affymetrix Targeted Genotyping 3K Chip array with 460 ONFH patients and 300 control subjects. We showed that single nucleotide polymorphisms (SNPs) in the genes TF, VEGFC, IGFBP3, and ACE were associated with an increased risk of ONFH. On the other hand, SNPs in the KDR and NRP1 genes were associated with protection against ONFH. The most important finding was that one SNP (rs2453839) in the IGFBP3 gene was significantly associated with a higher risk of ONFH (P = 0.0061, OR 7.74). In subgroup analysis, most candidate gene variations that were associated with ONFH occurred in the idiopathic subgroup. Among other SNPs, ACE SNPs were associated with steroid-induced ONFH (P = 0.0018-0.0037, OR ＞ 3). Collectively, our findings suggest that genetic variations in angiogenesis-and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population.

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“…cDNA was synthesised from RNA samples of each group at the same time to limit differences in the efficiency of the cDNA synthesis. Synthesised cDNA was amplified by PCR using mRNA-specific primers to generate products corresponding to mRNA encoding human ALP, collagen type I alpha chain (COL1A) 1, COL1A2, IGF-I, IGF-II, OCN, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) using reaction mixtures and conditions as previously detailed [16,24,27,30]. Amplification of GAPDH served as an internal positive control and allowed normalisation of the various mRNA levels against the total mRNA content in the samples.…”

Section: Methodsmentioning

confidence: 99%

Untitled

et al. 2006

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Previous studies have shown a generalised increase in bone mass in patients with osteoarthritis (OA). Using molecular histomorphometry, this study examined the in vivo expression of mRNA encoding bone anabolic factors and collagen type I genes (COL1A1, COL1A2) in human OA and non-OA bone. Bone samples were obtained from the intertrochanteric (IT) region of the proximal femur, a skeletal site distal to the active site of disease, from individuals with hip OA at joint replacement surgery and from autopsy controls. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (OCN) (p < 0.0001), osteopontin (p < 0.05), COL1A1 (p < 0.0001), and COL1A2 (p < 0.002) in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1/COL1A2 mRNA was almost twofold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type I homotrimer at the distal site. Insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor-β1 mRNA levels were similar between OA and control bone. Bone histomorphometric analysis indicated that OA IT bone had increased surface density of bone (p < 0.0003), increased trabecular number (Tb.N) (p < 0.0003), and decreased trabecular separation (Tb.Sp) (p < 0.0001) compared to control bone. When the molecular and histomorphometric data were plotted, positive associations were observed in the controls for OCN/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) versus bone tissue volume (r = 0.82, p < 0.0007) and OCN/ GAPDH versus Tb.N (r = 0.56, p < 0.05) and a negative association was observed for OCN/GAPDH versus Tb.Sp (r = -0.64, p < 0.02). These relationships were not evident in trabecular bone from patients with OA, suggesting that bone regulatory processes leading to particular trabecular structures may be altered in this disease. The finding of differential gene expression, as well as architectural changes and differences in molecular histomorphometric associations between OA and controls, at a skeletal site distal to the active site of joint degeneration supports the concept of generalised involvement of bone in the pathogenesis of OA.

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Identification of differentially expressed genes between osteoarthritic and normal trabecular bone from the intertrochanteric region of the proximal femur using cDNA microarray analysis

Cited by 21 publications

References 56 publications

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis

Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head

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