title: Creating an Animal Model of Tendinopathy by Inducing Chondrogenic Differentiation with Kartogenin.
abstract: Previous animal studies have shown that long term rat treadmill running induces over-use tendinopathy, which manifests as proteoglycan accumulation and chondrocytes-like cells within the affected tendons. Creating this animal model of tendinopathy by long term treadmill running is however time-consuming, costly and may vary among animals. In this study, we used a new approach to develop an animal model of tendinopathy using kartogenin (KGN), a bio-compound that can stimulate endogenous stem/progenitor cells to differentiate into chondrocytes. KGN-beads were fabricated and implanted into rat Achilles tendons. Five weeks after implantation, chondrocytes and proteoglycan accumulation were found at the KGN implanted site. Vascularity as well as disorganization in collagen fibers were also present in the same site along with increased expression of the chondrocyte specific marker, collagen type II (Col. II). In vitro studies confirmed that KGN was released continuously from KGN-alginate in vivo beads and induced chondrogenic differentiation of tendon stem/progenitor cells (TSCs) suggesting that chondrogenesis after KGN-bead implantation into the rat tendons is likely due to the aberrant differentiation of TSCs into chondrocytes. Taken together, our results showed that KGN-alginate beads can be used to create a rat model of tendinopathy, which, at least in part, reproduces the features of over-use tendinopathy model created by long term treadmill running. This model is mechanistic (stem cell differentiation), highly reproducible and precise in creating localized tendinopathic lesions. It is expected that this model will be useful to evaluate the effects of various topical treatments such as NSAIDs and platelet-rich plasma (PRP) for the treatment of tendinopathy.
authors: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.|Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Ting
authors: T
authors: Yuan
authors: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
authors: Jianying
authors: J
authors: Zhang
authors: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
authors: Guangyi
authors: G
authors: Zhao
authors: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
authors: Yiqin
authors: Y
authors: Zhou
authors: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Chang-Qing
authors: CQ
authors: Zhang
authors: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
authors: James H-C
authors: JH
authors: Wang
mesh_terms: D000125:Achilles Tendon / Q000187:drug effects / Q000473:pathology; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D010795:Phthalic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D052256:Tendinopathy / Q000139:chemically induced / Q000473:pathology*
chemical_list: D000813:Anilides; D010795:Phthalic Acids; C572342:kartogenin