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Perlecan‐Containing Pericellular Matrix Regulates Solute Transport and Mechanosensing Within the Osteocyte Lacunar‐Canalicular System
Author(s) -
Wang Bin,
Lai Xiaohan,
Price Christopher,
Thompson William R,
Li Wen,
Quabili Tonima R,
Tseng WeiJu,
Liu Xiaowei Sherry,
Zhang Hong,
Pan Jun,
KirnSafran Catherine B,
FarachCarson Mary C,
Wang Liyun
Publication year - 2014
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2105
Subject(s) - perlecan , osteocyte , bone canaliculus , fluorescence recovery after photobleaching , chemistry , microbiology and biotechnology , biophysics , mechanotransduction , matrix (chemical analysis) , trpv4 , proteoglycan , extracellular matrix , transient receptor potential channel , anatomy , osteoblast , biology , biochemistry , in vitro , receptor , chromatography , membrane
The 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. © 2014 American Society for Bone and Mineral Research.