Perlecan-Containing Pericellular Matrix Regulates Solute Transport and Mechanosensing Within the Osteocyte Lacunar-Canalicular System

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dc.citation.firstpage878en_US
dc.citation.issueNumber4en_US
dc.citation.journalTitleJournal of Bone and Mineral Researchen_US
dc.citation.lastpage891en_US
dc.citation.volumeNumber29en_US
dc.contributor.authorWang, Binen_US
dc.contributor.authorLai, Xiaohanen_US
dc.contributor.authorPrice, Christopheren_US
dc.contributor.authorThompson, William R.en_US
dc.contributor.authorLi, Wenen_US
dc.contributor.authorQuabili, Tonima R.en_US
dc.contributor.authorTseng, Wei-Juen_US
dc.contributor.authorLiu, Xiaowei Sherryen_US
dc.contributor.authorZhang, Hong-Yien_US
dc.contributor.authorPan, Junen_US
dc.contributor.authorKirn-Safran, Catherine B.en_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.contributor.authorWang, Liyunen_US
dc.date.accessioned2017-08-04T12:29:41Zen_US
dc.date.available2017-08-04T12:29:41Zen_US
dc.date.issued2014en_US
dc.description.abstractThe pericellular matrix (PCM), a thin coating surrounding nearly all mammalian cells, plays a critical role in many cell-surface phenomena. In osteocytes, the PCM is believed to control both “outside-in” (mechanosensing) and “inside-out” (signaling molecule transport) processes. However, the osteocytic PCM is challenging to study in situ because it is thin (∼100 nm) and enclosed in mineralized matrix. To this end, we recently developed a novel tracer velocimetry approach that combined fluorescence recovery after photobleaching (FRAP) imaging with hydrodynamic modeling to quantify the osteocytic PCM in young murine bone. In this study, we applied the technique to older mice expressing or deficient for perlecan/HSPG2, a large heparan-sulfate proteoglycan normally secreted in osteocytic PCM. The objectives were (1) to characterize transport within an altered PCM; (2) to test the sensitivity of our approach in detecting the PCM alterations; and (3) to dissect the roles of the PCM in osteocyte mechanosensing. We found that: (1) solute transport increases in the perlecan-deficient (hypomorphic [Hypo]) mice compared with control mice; (2) PCM fiber density decreases with aging and perlecan deficiency; (3) osteocytes in the Hypo bones are predicted to experience higher shear stress (+34%), but decreased fluid drag force (−35%) under 3-N peak tibial loading; and (4) when subjected to tibial loading in a preliminary in vivo experiment, the Hypo mice did not respond to the anabolic stimuli as the CTL mice did. These findings support the hypothesis that the PCM fibers act as osteocyte's sensing antennae, regulating load-induced cellular stimulations and thus bone's sensitivity and in vivo bone adaptation. If this hypothesis is further confirmed, osteocytic PCM could be new targets to develop osteoporosis treatments by modulating bone's intrinsic sensitivity to mechanical loading and be used to design patient-specific exercise regimens to promote bone formation.en_US
dc.identifier.citationWang, Bin, Lai, Xiaohan, Price, Christopher, et al.. "Perlecan-Containing Pericellular Matrix Regulates Solute Transport and Mechanosensing Within the Osteocyte Lacunar-Canalicular System." <i>Journal of Bone and Mineral Research,</i> 29, no. 4 (2014) Wiley: 878-891. https://doi.org/10.1002/jbmr.2105.en_US
dc.identifier.digitalPerlecan-containing_pericellular_matrixen_US
dc.identifier.doihttps://doi.org/10.1002/jbmr.2105en_US
dc.identifier.urihttps://hdl.handle.net/1911/96575en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Society for Bone and Mineral Research.en_US
dc.titlePerlecan-Containing Pericellular Matrix Regulates Solute Transport and Mechanosensing Within the Osteocyte Lacunar-Canalicular Systemen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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