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Bone is a rigid tissue that performs several key functions: it supports the body; it provides a point of attachment for tendons; it protects the internal organs; it produces blood cells; and it stores key minerals such as calcium and phosphorus. Throughout life, bone is remodeled by the activity of osteoblasts and osteoclasts. Osteoblasts are responsible for the synthesis of bone, while osteoclasts resorb bone tissue. A carefully controlled balance of these activities underlies bone remodeling and an imbalance can result in disorders such as osteoporosis, which weakens bones.
Osteoblasts and osteoclasts are derived from different cell precursors - mesenchymal and hematopoietic stem cells (MSCs and HSCs), respectively. Differentiation of HSCs to osteoclasts involves a number of cytokines such as bone morphogenetic protein (BMP) and TNF-α. Rho kinase (ROCK) inhibition may also stimulate osteoblast differentiation. Osteoblasts and osteoclasts are responsible for bone repair and growth, as well as the maintenance of bone density.
Loss of bone density normally occurs after the age of 35, and is a natural part of ageing. Bone turnover is regulated by a number of factors, including estrogen, nitric oxide and calcium-regulated calcium channels. However, bone loss may also be a result of metabolic bone disease, a term that describes a number of disorders resulting from mineral abnormalities in bone tissue. These include osteoporosis, Paget's disease of bone, osteomalacia and rickets.
Osteoporosis is relatively common, particularly in post-menopausal women, and can result in an increased likelihood of bone fracture. Osteomalacia and rickets describe deficiencies in bone mineralization in adults and children, respectively. Paget's disease of bone results from increased bone resorption by osteoclasts, followed by rapid, disorganized bone deposition by osteoblasts. The resulting tissue is larger and weaker than normal bone.
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.