title: Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.
abstract: Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Dai
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Pi
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Duan
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Ao
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000378:metabolism / Q000473:pathology; D000070598:Anterior Cruciate Ligament Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics*; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013710:Tendons / Q000378:metabolism / Q000473:pathology; D013718:Tensile Strength; D013977:Tibia / Q000378:metabolism / Q000473:pathology
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; D034741:RNA, Small Interfering; C493717:Runx2 protein, rat; D015675:Osteocalcin