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Population ageing will likely lead to an increase in the prevalence of bone diseases such as osteoporosis and osteoarthritis, thereby increasing the financial burden among both diseased and unaffected people. Although significant progress has been made in understanding bone health in biomedical applications, more research is needed to address unmet needs and understand healthy bone homeostasis. This special issue of Experimental & Molecular Medicine includes a collection of review articles on cutting-edge topics related to healthy bone homeostasis.
A deeper understanding of skeletal tissue development and improvements in tissue engineering will help pluripotent stem cell (PSC) therapies to reach their full potential for skeletal repair. The paraxial mesoderm, an embryonic germ layer, is crucial to the formation of healthy axial skeleton. Shoichiro Tani at the University of Tokyo, Japan, and co-workers reviewed current understanding of paraxial mesoderm development and studies involving in vitro PSC skeletal modeling. The formation of the paraxial mesoderm and associated connective tissues comprises multiple stages, and studies in vertebrate embryos have uncovered critical signaling pathways and cellular components important to PSC modeling. Although many individual cellular components can now be modeled, it remains challenging to recreate three-dimensional skeletal tissues. Such an achievement would facilitate a functioning model of bone metabolism, the next step in achieving skeletal regeneration.
Therapies that modulate the activity of the regulatory protein RUNX2 could potentially restore normal bone development in a range of skeletal disorders, and repair damage from injury or degeneration. RUNX2 is an essential regulator of genes that drive formation of bone-producing osteoblast cells. It can be activated or inactivated by the enzymatic addition of various chemical groups. Hyun-Mo Ryoo and colleagues at Seoul National University, South Korea, review the role of such modifications in bone disorders. For example, the loss of modifications activated by RUNX2 can result in delayed integration of the bones that form the skull. The authors highlight potential opportunities to manipulate these modification processes to treat this and other developmental disorders. Similar strategies could also promote repair of fractures or counter osteoporotic bone loss.
Maintaining normal bone structure and strength depends on a group of signaling proteins called cytokines that bind to receptor molecules on cell surfaces. Natalie Sims at St. Vincent’s Institute of Medical Research and The University of Melbourne in Australia reviews the role of cytokines in a specific signaling pathway in bone development and disease. Two of the proteins in this pathway respond to cytokine activity, whereas the third inhibits the cytokines’ effects. Studies in mice and humans have identified links between specific bone defects and spontaneous or experimentally induced mutations in the genes that code for the three proteins. The review covers the significance of recent findings to several types of cells that form new bone, degrade bone as part of normal bone turnover, and sustain the structure of bone and cartilage.
Selenium, a micronutrient found in brazil nuts, shiitake mushrooms, and most meats, may aid in treating joint diseases, including the most common form of arthritis, osteoarthritis (OA). In addition to thyroid hormone metabolism and immunity, selenium is important in antioxidant defense. Oxidative damage can destroy cartilage and harm joints, and selenium deficiency is implicated in several joint diseases. Jin-Hong Kim at Seoul National University in South Korea and co-workers reviewed selenium metabolism, focusing on OA and and Kashin–Beck disease, a skeletal development disorder prevalent in selenium-deficient areas of northeast Asia. They report that selenium-containing proteins protect cells against oxidative damage and that selenium is crucial to cartilage production. Further investigation of selenium metabolism may point the way to new treatments for OA and other joint diseases.