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Timothy Dreyer, Jacob Keen, Leah Wells, and Scott Roberts

As a key regulator of bone homeostasis, sclerostin has garnered a lot of interest over the last two decades. Although sclerostin is primarily expressed by osteocytes and is well known for its role in bone formation and remodelling, it is also expressed by a number of other cells and potentially plays a role in other organs. Herein, we aim to bring together recent sclerostin research and discuss the effect of sclerostin on bone, cartilage, muscle, liver, kidney and the cardiovascular and immune systems. Particular focus is placed on its role in disease, such as osteoporosis and myeloma bone disease, and the novel development of sclerostin as a therapeutic target. Anti-sclerostin antibodies have recently been approved for treatment of osteoporosis. However, a cardiovascular signal was observed, prompting extensive research into the role of sclerostin in vascular and bone tissue crosstalk. Heightened sclerostin expression in chronic kidney disease resulted in investigation of its role in liver-lipid-bone interactions, and recent discovery of sclerostin as a myokine prompted new research into sclerostin within the bone-muscle relationship. Clearly the effects of sclerostin reach beyond that of bone alone. We further summarise recent developments in the use of sclerostin as a potential therapeutic for osteoarthritis, osteosarcoma and sclerosteosis. Together, these new treatments and discoveries illustrate progress within the field, however, also highlight remaining gaps in our knowledge.