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The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small(More)
Mechanical unloading, such as in a microgravity environment in space or during bed rest (for patients who require prolonged bed rest), leads to a decrease in bone mass because of the suppression of bone formation and the stimulation of bone resorption. To address the challenges presented by a prolonged stay in space and the forthcoming era of a super-aged(More)
NF-kappaB is a pleiotropic transcription factor, which regulates osteoclast formation, function, and survival. The finding that the deletion of both NF-kappaB p50 and p52 subunits resulted in osteopetrosis due to the absence of osteoclasts was followed by the observation that NF-kappaB is essential for RANK-expressing osteoclast precursors to differentiate(More)
Peptides are attractive as novel therapeutic reagents, since they are flexible in adopting and mimicking the local structural features of proteins. Versatile capabilities to perform organic synthetic manipulations are another unique feature of peptides compared to protein-based medicines, such as antibodies. On the other hand, a disadvantage of using a(More)
Osteoclasts are multinucleated cells of hematopoietic origin which are unique in their ability to resorb bone. Osteoclasts are generated from myeloid progenitors through a progression that involves the fusion of mononuclear precursor cells. The identification of RANK-RANKL signaling as the main signal regulating osteoclast differentiation was a major(More)
Prostaglandins (PGs) are key regulatory factors that affect bone metabolism. Prostaglandin E(2) (PGE(2)) regulates bone resorption and bone formation. Prostacyclin (PGI(2)) is one of the major products derived from arachidonic acid by the action of cyclooxygenase and PGI(2) synthase (PGIS). Unlike PGE(2), there are few reports about the role of PGI(2) in(More)
TNF-alpha is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-alpha. Several lines of evidence show inhibition of osteoblastogenesis by TNF-alpha in vitro. Therefore,(More)
Bone degenerative diseases, including osteoporosis, impair the fine balance between osteoclast bone resorption and osteoblast bone formation. Single-agent therapy for anabolic and anticatabolic effects is attractive as a drug target to ameliorate such conditions. Inhibition of nuclear factor (NF)-κB reduces the osteoclast bone resorption. The role of NF-κB(More)
The classical NF-kappaB pathway plays an important role in osteoclast formation and differentiation; however, the role of NF-kappaB in osteoclast bone-resorbing activity is not well understood. To elucidate whether NF-kappaB is important for osteoclast bone-resorbing activity, we used a selective peptide inhibitor of the classical NF-kappaB pathway named(More)
Confocal laser microscopy is a well-recognized research tool in the fields of biological and material science which enables high-resolution images of samples with minimum requirements for specimen preparation. Here we introduce an innovative technique for the 3-D description and measurement of resorption pits using Super Depth Surface Profile Measurement(More)