Abstract
The adenosine monophosphate (AMP)–activated protein kinase (AMPK) was initially identified as an enzyme acting as an “energy sensor” in maintaining energy homeostasis via serine/threonine phosphorylation when low cellular adenosine triphosphate (ATP) level was sensed. AMPK participates in catabolic and anabolic processes at the molecular and cellular levels and is involved in appetite-regulating circuit in the hypothalamus. AMPK signaling also modulates energy metabolism in organs such as adipose tissue, brain, muscle, and heart, which are highly dependent on energy consumption via adjusting the AMP/ADP:ATP ratio. In clinics, biguanides and thiazolidinediones are prescribed to patients with metabolic disorders through activating AMPK signaling and inhibiting complex I in the mitochondria, leading to a reduction in mitochondrial respiration and elevated ATP production. The role of AMPK in mediating skeletal development and related diseases remains obscure. In this review, in addition to discuss the emerging advances of AMPK studies in energy control, we will also illustrate current discoveries of AMPK in chondrocyte homeostasis, osteoarthritis (OA) development, and the signaling interaction of AMPK with other pathways, such as mTOR (mechanistic target of rapamycin), Wnt, and NF-κB (nuclear factor κB) under OA condition.
Highlights
Advanced technology and medical therapy in health care are highly demanded in the era after the Millennium
OA has been observed for centuries but still has not been solved yet because of its unclear pathogenicity, its association with age, mechanical loading, and hereditary has been explained to some extent
AMPK, as it has been studied for decades, gained significant attention due to its vital role in maintaining energy balance in the body
Summary
A few attempts were conducted and tried to study the functions of AMPK in tissue distribution associated with metabolic physiological conditions: glycogen synthase in skeletal muscle related to GLUT4 translocation and lipolysis and lipogenesis in isolated rat adipocytes with AICAR (Steinberg and Carling, 2019). After the Millennium, with the great leap forward of science and technology, the scientists have ushered in a prosperous age that advanced technology applied to explore comprehensive molecular mechanisms in detail In this transition period, gamma subunit of AMPK had been revealed and implied its function in mediating energy; peroxisome proliferatoractivated receptor δ (PPARδ) agonists were applied in few studies. Studies on the functional activities and metabolic balance of AMPK in other organs are needed
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