CaMKK2 Signaling in Metabolism and Skeletal Disease: a New Axis with Therapeutic Potential

• Published in: Current osteoporosis reports Vol. 17; no. 4; pp. 169 - 177
• Main Authors: Williams, Justin N., Sankar, Uma
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019
• Subjects: Epidemiology; Medicine; Medicine & Public Health; Orthopedics; Section Editors; Skeletal Biology and Regulation (M Forwood and A Robling; Topical Collection on Skeletal Biology and Regulation; Skeletal disease; Fracture healing; Diabetic osteopathy; Diabetes; CaMKK2
• ISSN: 1544-1873; 1544-2241
• DOI: 10.1007/s11914-019-00518-w

Purpose of Review Age and metabolic disorders result in the accumulation of advanced glycation endproducts (AGEs), oxidative stress, and inflammation, which cumulatively cause a decline in skeletal health. Bone becomes increasingly vulnerable to fractures and its regenerative capacity diminishes under such conditions. With a rapidly aging population in the USA and the global increase in diabetes, efficacious, multi-dimensional therapies that can treat or prevent skeletal diseases associated with metabolic dysfunction and inflammatory disorders are acutely needed. Recent Findings Ca 2+ /calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of nutrient intake, glucose metabolism, insulin production, and adipogenesis. Recent studies suggest a pivotal role for CaMKK2 in bone metabolism, fracture healing, and inflammation. Summary Aside from rekindling previous concepts of CaMKK2 as a potent regulator of whole-body energy homeostasis, this review emphasizes CaMKK2 as a potential therapeutic target to treat skeletal diseases that underlie metabolic conditions and inflammation.