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2017 ; 74
(9
): 1649-1657
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Wnt signaling and cellular metabolism in osteoblasts
#MMPMID27888287
Karner CM
; Long F
Cell Mol Life Sci
2017[May]; 74
(9
): 1649-1657
PMID27888287
show ga
The adult human skeleton is a multifunctional organ undergoing continuous
remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite
balance between bone resorption by osteoclasts and bone formation by osteoblasts;
disturbance of such balance is the root cause for various bone disorders
including osteoporosis. To develop effective and safe therapeutics to modulate
bone formation, it is essential to elucidate the molecular mechanisms governing
osteoblast differentiation and activity. Due to their specialized function in
collagen synthesis and secretion, osteoblasts are expected to consume large
amounts of nutrients. However, studies of bioenergetics and building blocks in
osteoblasts have been lagging behind those of growth factors and transcription
factors. Genetic studies in both humans and mice over the past 15 years have
established Wnt signaling as a critical mechanism for stimulating osteoblast
differentiation and activity. Importantly, recent studies have uncovered that Wnt
signaling directly reprograms cellular metabolism by stimulating aerobic
glycolysis, glutamine catabolism as well as fatty acid oxidation in
osteoblast-lineage cells. Such findings therefore reveal an important regulatory
axis between bone anabolic signals and cellular bioenergetics. A comprehensive
understanding of osteoblast metabolism and its regulation is likely to reveal
molecular targets for novel bone therapies.
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