Justin N Williams1, Uma Sankar2. 1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5055, Indianapolis, IN, 46202, USA. 2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5055, Indianapolis, IN, 46202, USA. usankar@iupui.edu.
Abstract
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: Ca2+/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. 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.
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:Ca2+/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. 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.
Authors: Mohd Altaf Najar; D A B Rex; Prashant Kumar Modi; Nupur Agarwal; Shobha Dagamajalu; Gayathree Karthikkeyan; Manavalan Vijayakumar; Aditi Chatterjee; Uma Sankar; T S Keshava Prasad Journal: J Cell Commun Signal Date: 2020-11-02 Impact factor: 5.782
Authors: Hal E Broxmeyer; James Ropa; Maegan L Capitano; Scott Cooper; Luigi Racioppi; Uma Sankar Journal: Stem Cell Rev Rep Date: 2022-03-09 Impact factor: 6.692
Authors: Ian G Mills; Emma Evergren; Lorna M Stewart; Lisa Gerner; Mandy Rettel; Frank Stein; James F Burrows Journal: Cell Death Dis Date: 2021-11-01 Impact factor: 8.469