Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). == Conclusion == Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. FDR = 6. 35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). == Conclusion == Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res2016; 5: 594601. FRP-1 DOI: 10. 1302/2046-3758. 512. BJR-2016-0073. R1. Keywords: Integrated analysis, Microarray, Osteoporosis, Peripheral blood mononuclear cells, Differentially expressed genes == Article focus == To screen the altered gene expression profile Pepstatin A in peripheral blood mononuclear cells of patients with osteoporosis. To interpret the biological roles of the identified differentially expressed genes in patients with osteoporosis. To identify the potential candidate genes in osteoporosis. == Key messages == A total of 1125 genes were found to be signicantly differentially expressed in peripheral blood monocytes (PBMs) between osteoporosis patients and normal controls, with 373 upregulated Pepstatin A and 752 downregulated genes. Some genes, such as nuclear Pepstatin A receptor interacting protein 1, interleukin 1 receptor associated kinase 3, and ubiquitin specific peptidase 9 X-linked, were highly correlated with the development of osteoporosis. The significantly enriched pathways, such as the mitogen-activated protein kinase and the calcium signalling pathways, may involve in osteoporosis through osteoblast differentiation and bone formation. == Strengths and limitations == This study revealed the gene Pepstatin A expression profiles in PBMs between osteoporosis patients and normal controls with large statistical power. The gene function analysis of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. However , the differentially expressed genes in our study are predicted without experimental evidence, such as reverse transcription polymerase chain reaction and Western blot. Therefore , further research is needed to uncover gene functions in osteoporosis pathogenesis. == Introduction == Osteoporosis is one of the most common and serious metabolic bone diseases, which affects 200 million people worldwide, among which 80% Pepstatin A are women aged 60 years or older. 1Osteoporosis manifests clinically by reduced bone mass, a decreased amount of normally mineralised bone and microarchitectural deterioration of bone tissues, accounting for an increase in susceptibility to fracture. 2Genetic predisposition, combined with advanced age, gender, immobilisation, and other risk factors, contribute to the development of osteoporosis. 3Genome-wide association studies have been performed to search for an association between bone mineral density (BMD) and osteoporosis in twin and family studies. 4, 5A meta-analysis of genome-wide association studies identified 56 low BMD-associated loci, and 14 loci which were associated with risk of fracture. 6The association of vitamin D (1, 25- dihydroxyvitamin D3) receptor, oestrogen receptor 1 (ER) and LDL receptor related protein 5 with osteoporosis, has been most widely studied as candidate genetic genes. The imbalance between bone resorption (by osteoclasts) and bone formation (by osteoblasts) is a key pathophysiological mechanism of osteoporosis as a consequence of pathologically prolonging the life span of osteoclasts and early apoptosis of osteoblasts and osteocytes. 7-9Circulating monocytes play important roles in this process, as they differentiate into osteoclasts to be involved in bone resorption, 10, 11and produce a wide variety of factors for osteoclastogenesis and bone resorption. 12Osteoclasts from circulating mononuclear cells of osteoporotic patients demonstrated increased bone resorption activity compared with normal controls. 13Primary osteoporosis is related either to the postmenopausal state or advanced age (senile osteoporosis) due to the cellular changes associated with oestrogen deciency and ageing. For postmenopausal osteoporosis, oestrogen deficiency leads to upregulation of receptor activator of nuclear factor-kappa ligand (RANKL) and tumour necrosis factor-, resulting in excessive bone resorption and rapid bone loss. 14For senile osteoporosis, there is also a signicant reduction in bone formation due to osteoblastic dysfunction. Osteoblasts and adipocytes both differentiate from mesenchymal originate cells (MSCs), and there is a.