A Central Role for p53 in Osteoporosis?
Osteoporosis is the name given to the advanced stages of the characteristic age-related loss of bone strength and density. Bone tissue is constantly remodeled, created by osteoblasts and broken down by osteoclasts. With advancing age, the activity of osteoclasts begins to dominate, and thus bone becomes ever weaker and lighter, with eventually disastrous consequences. There are many possible contributing causes for this imbalance between cell types, most of which are present in all older individuals. It is therefore interesting to speculate on why only some people progress to clinical osteoporosis. Hence studies of the sort noted here, in which researchers attempt to pick apart the complexities of the disease state, in search of noteworthy differences between older individuals with and without clinical osteoporosis.
Osteoporosis is a metabolic disease characterized by decreased bone mass per unit volume, despite the bone tissue having normal calcification and a normal ratio of calcium salt and matrix. As one of the most commonly occurring chronic diseases among the elderly, osteoporosis has become a serious problem for public health care systems. The pathogenesis of osteoporosis has not yet been fully elucidated. Factors that inhibit osteogenesis, promote bone resorption, or cause bone microstructural destruction may play a role in the development of osteoporosis, and a variety of genes may be directly or indirectly involved.
In the present study, we applied bioinformatic analysis of an osteoporosis microarray dataset retrieved from the Gene Expression Omnibus (GEO) to explore the mechanisms underlying osteoporosis. We analyzed the interactions among involved proteins and ranking the top 10 hub genes. The identified hub genes were TP53, MAPK1, CASP3, CTNNB1, CCND1, NOTCH1, CDK1, IGF1, ERBB2, and CYCS. Moreover, we found that nearly all of the top 10 hub genes were involved in the top five enriched Gene Ontology terms or KEGG pathways, indicating their potential roles in osteoporosis progression. Consistent with our findings, a number of studies have previously reported the involvement of TP53, MAPK1, CASP3, CTNNB1, CCND1, NOTCH1, CDK1, IGF1, ERBB2 in osteoporosis or osteogenesis.
P53 had the highest degree score in the network, indicating it may play a central role during the development of osteoporosis. P53 is encoded by the tumor suppressor gene TP53 and suppresses tumor growth by slowing cell growth and division. In the present study, it is found that serum p53 levels are increased in osteoporosis patients, and knocking down p53 partially reversed decreases in bone mineral density in vitro and in vivo. In addition, GO and KEGG enrichment analyses indicate that p53 is involved in "the cancer pathway," "proteoglycans in cancer pathway," and "P53 signaling pathway." We therefore suggest that p53 may contribute to the pathogenesis of osteoporosis via these pathways.