title: The paratenon contributes to scleraxis-expressing cells during patellar tendon healing.
abstract: The origin of cells that contribute to tendon healing, specifically extrinsic epitenon/paratenon cells vs. internal tendon fibroblasts, is still debated. The purpose of this study is to determine the location and phenotype of cells that contribute to healing of a central patellar tendon defect injury in the mouse. Normal adult patellar tendon consists of scleraxis-expressing (Scx) tendon fibroblasts situated among aligned collagen fibrils. The tendon body is surrounded by paratenon, which consists of a thin layer of cells that do not express Scx and collagen fibers oriented circumferentially around the tendon. At 3 days following injury, the paratenon thickens as cells within the paratenon proliferate and begin producing tenascin-C and fibromodulin. These cells migrate toward the defect site and express scleraxis and smooth muscle actin alpha by day 7. The thickened paratenon tissue eventually bridges the tendon defect by day 14. Similarly, cells within the periphery of the adjacent tendon struts express these markers and become disorganized. Cells within the defect region show increased expression of fibrillar collagens (Col1a1 and Col3a1) but decreased expression of tenogenic transcription factors (scleraxis and mohawk homeobox) and collagen assembly genes (fibromodulin and decorin). By contrast, early growth response 1 and 2 are upregulated in these tissues along with tenascin-C. These results suggest that paratenon cells, which normally do not express Scx, respond to injury by turning on Scx and assembling matrix to bridge the defect. Future studies are needed to determine the signaling pathways that drive these cells and whether they are capable of producing a functional tendon matrix. Understanding this process may guide tissue engineering strategies in the future by stimulating these cells to improve tendon repair.
authors.affiliation: Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, United States of America. dyment@uchc.edu
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Dyment
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Namdar
authors.initials: N
authors.lastname: Kazemi
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Aschbacher-Smith
authors.forename: Keith
authors.initials: K
authors.lastname: Kenter
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Breidenbach
authors.forename: Jason T
authors.initials: JT
authors.lastname: Shearn
authors.forename: Christopher
authors.initials: C
authors.lastname: Wylie
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
authors.forename: David L
authors.initials: DL
authors.lastname: Butler
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D000071235:Fibromodulin; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D017847:Patellar Ligament / Q000293:injuries* / Q000378:metabolism*; D010641:Phenotype; D025341:Principal Component Analysis; D011509:Proteoglycans / Q000096:biosynthesis; D019063:Tenascin / Q000096:biosynthesis; D013708:Tendon Injuries / Q000378:metabolism*; D013997:Time Factors; D014945:Wound Healing / Q000235:genetics
chemical_list: D000199:Actins; D051792:Basic Helix-Loop-Helix Proteins; D003094:Collagen; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D049452:Green Fluorescent Proteins; D011509:Proteoglycans; D019063:Tenascin; C000604332:Fmod protein, mouse; C503815:Scx protein, mouse
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