title: IL-1β irreversibly inhibits tenogenic differentiation and alters metabolism in injured tendon-derived progenitor cells in vitro.
abstract: Tendon injuries are common, and the damaged tendon often turns into scar tissue and never completely regains the original biomechanical properties. Previous studies have reported that the mRNA levels of inflammatory cytokines such as IL-1β are remarkably up-regulated in injured tendons. To examine how IL-1β impacts tendon repair process, we isolated the injured tendon-derived progenitor cells (inTPCs) from mouse injured Achilles tendons and studied the effects of IL-1β on the inTPCs in vitro. IL-1β treatment strongly reduced expression of tendon cell markers such as scleraxis and tenomodulin, and also down-regulated gene expression of collagen 1, collagen 3, biglycan and fibromodulin in inTPCs. Interestingly, IL-1β stimulated lactate production with increases in hexokinase II and lactate dehydrogenase expression and a decrease in pyruvate dehydrogenase. Inhibition of lactate production restored IL-1β-induced down-regulation of collagen1 and scleraxis expression. Furthermore, IL-1β significantly inhibited adipogenic, chondrogenic and osteogenic differentiation of inTPCs. Interestingly, inhibition of tenogenic and adipogenic differentiation was not recovered after removal of IL-1β while chondrogenic and osteogenic differentiation abilities were not affected. These findings indicate that IL-1β strongly and irreversibly impairs tenogenic potential and alters glucose metabolism in tendon progenitors appearing in injured tendons. Inhibition of IL-1β may be beneficial for maintaining function of tendon progenitor cells during the tendon repair process.
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Translational Research Program in Pediatric Orthopaedics, Division of Orthopedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Kairui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, Division of Orthopedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: yubinol@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, Division of Orthopedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: iwamotom1@email.chop.edu.
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000502:physiology*; D051379:Mice; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013710:Tendons / Q000166:cytology / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta; D005947:Glucose
keywords: IL-1β; Injury; Progenitor; Tendon