Editorial: lipid kinases and bone homeostasis: lessons learned from phosphoinositide 3-kinase isoform-specific knockouts.
Editorial: lipid kinases and bone homeostasis: lessons learned from phosphoinositide 3-kinase isoform-specific knockouts.
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社论：脂质激酶和骨稳态：从磷酸肌醇 3-激酶亚型特异性敲除中吸取的教训。
DOI：
10.1002/art.38661
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Humphrey,MaryBeth
中科院分区：
文献类型：
--
作者：
Xing,Junjie;Humphrey,MaryBeth
Bone homeostasis is maintained throughout life by coordinated osteocyte regulation of bone resorption by osteoclasts and bone formation by osteoblasts. Many pathologic bone states such as osteoporosis, inflammatory arthritis, and bone metastasis have increased numbers, survival, or function of osteoclasts resulting in enhanced bone resorption outpacing bone formation. Differentiation, survival, recruitment, and resorptive activity of osteoclasts and their precursors are highly regulated by intracellular signals stimulated by soluble mediators, extracellular matrix, and adjacent cells. In this issue of Arthritis & Rheumatology, Gyoőri and colleagues describe a specific role for the enzyme phosphoinositide 3-kinase β (PI3Kβ) in the regulation of osteoclast-mediated bone resorption (1), suggesting that a specific inhibitor of this enzyme isoform may be a novel antiresorptive agent.Osteoclasts are multinucleated cells containing numerous mitochondria and lysosomes, and they are adherent to bone surfaces. Osteoclast migration, polarization, and resorption are dependent on effective actin cytoskeleton reorganization into specialized podosomes, podosome belts, and actin rings. When attached to bone, mature osteoclasts form stable sealing zones consisting of an actin ring and ruffled borders made of infoldings of plasma membrane. During the process of bone resorption, the osteoclast cytoskeleton further rearranges such that secretory vesicles polarize toward and insert into the ruffled border plasma membrane to deliver their cargo of matrix-degrading molecules, including collagenase and other enzymes, into resorption lacunae (2).
