"A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis"
作者全名："Wang, Xiaofang; Ma, Yufei; Chen, Jie; Liu, Yujiao; Liu, Guangliang; Wang, Pengtao; Wang, Bo; Taketo, Makoto M.; Bellido, Teresita; Tu, Xiaolin"
作者地址："[Wang, Xiaofang; Ma, Yufei; Chen, Jie; Liu, Yujiao; Liu, Guangliang; Wang, Pengtao; Wang, Bo; Tu, Xiaolin] Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China; [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan; [Bellido, Teresita] Univ Arkansas Med Sci, Dept Physiol & Cell Biol, Little Rock, AR 72223 USA; [Tu, Xiaolin] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA"
通信作者："Tu, XL (通讯作者)，Chongqing Med Univ, Inst Life Sci, Lab Skeletal Dev & Regenerat, Chongqing 400016, Peoples R China."
关键词：Decellularized matrix; Osteocyte; Wnt signaling; 3D printing; Regenerative repair; Metabolic and neurovascular organoid bone
摘要："Cell source is the key to decellularized matrix (DM) strategy. This study compared 3 cell types, osteocytes with/ without dominant active Wnt/beta-catenin signaling (daCO and WTO) and bone marrow stromal cells (BMSCs) for their DMs in bone repair. Decellularization removes all organelles and > 95% DNA, and retained > 74% collagen and > 71% GAG, maintains the integrity of cell basement membrane with dense boundaries showing oval and honeycomb structure in osteocytic DM and smooth but irregular shape in the BMSC-DM. DM produced higher cell survival rate (90%) and higher proliferative activity. In vitro, daCO-DM induces more and longer stress fibers in BMSCs, conducive to cell adhesion, spreading, and osteogenic differentiation. 8-wk after implantation of the critical-sized parietal bone defect model, daCO-DM formed tight structures, composed of a large number of densely-arranged type-I collagen under polarized light microscope, which is similar to and integrated with host bone. BV/TV (> 54%) was 1.5, 2.9, and 3.5 times of WTO-DM, BMSC-DM, and none-DM groups, and N.Ob/T.Ar (3.2 x 10(2)/mm(2)) was 1.7, 2.9, and 3.3 times. At 4-wk, daCO-DM induced osteoclastogenesis, 2.3 times higher than WTO-DM; but BMSC-DM or none-DM didn't. daCO-DM increased the expression of RANKL and MCSF, Vegfa and Angpt1, and Ngf in BMSCs, which contributes to osteoclastogenesis, angiogenesis, and neurogenesis, respectively. daCO-DM promoted H-type vessel formation and nerve markers beta 3-tubulin and NeuN expression. Conclusion: daCO-DM produces metabolic and neurovascularized organoid bone to accelerate the repair of bone defects. These features are expected to achieve the effect of autologous bone transplantation, suitable for transformation application."
基金机构："National Natural Science Foundation of China [U1601220, 81672118, 82072450, 82002310]; Chongqing Science and Technology Commission-Basic Science and Frontier Technology Key Project [cstc2015jcyjBX0119]; CQMU Program for Youth Innovation in Future Medicine [W0075]"
基金资助正文："This research was funded by the National Natural Science Foundation of China U1601220 (X.T.) ,81672118 (X.T.) , 82072450 (X.T.) , 82002310 (Y.M.) , Chongqing Science and Technology Commission-Basic Science and Frontier Technology Key Project cstc2015jcyjBX0119 (X.T.) , and CQMU Program for Youth Innovation in Future Medicine, W0075 (Y.M.) ."