Human bones are formed through intramembranous and endochondral ossification followed by a period of appositional growth. Skeletal homeostasis of cancellous/trabecular and cortical bone tissue is sustained through a lifelong biological process known as bone remodeling. Bone remodeling is the balanced-integrated function of osteocyte signaling, osteoblast bone formation, and osteoclast bone resorption. In this review, the autocrine and paracrine factors that control the rate of bone synthesis and resorption as they attribute to osteogenic cell differentiation, localization, and function are reviewed. These factors direct the transition between each phase of the remodeling process: activation, resorption, reversal, formation, and mineralization. The five primary intracellular signaling pathways that regulate osteogenic gene expression, cell function, localization, and survival include: Wnt/βcatenin, transforming growth factor-β, bone morphogenetic protein, arachidonic acid metabolism/prostaglandin synthesis, and receptor activator of nuclear factor κ B are also discussed. Several diseases are associated with dysregulated bone remodeling and aberrant signaling in osteogenic cells. Some hereditable and acquired genetic mutations result in skeletal diseases, like craniometaphyseal dysplasia, osteogenesis imperfecta, osteopetrosis, and myeloma bone disease. Other skeletal disorders are attributed to endogenous and exogenous induced hormonal imbalances, like postmenopausal osteoporosis or glucocorticoid steroid use, or cytokine imbalances that exacerbate inflammatory diseases, like rheumatoid arthritis. The role of excessive resorption and inadequate bone formation have in these diseases that may result in overall decreased skeletal tissue integrity, chronic pain, pathological bone fractures, and mortality are also examined.
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