Abstract
ABSTRACTRestoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12‐week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p<0.01) as well as sub‐failure biomechanical deficiencies. Although collagen fiber orientation appears overtly normal in the midsubstance, ablating Hh signaling reduces mineralized fibrocartilage by 32%, leading to less collagen embedded within mineralized tissue. Ablating Hh signaling also caused collagen fibers to coalesce at the insertion, which may explain in part the increased strains. These results indicate that Ihh signaling plays a critical role in the mineralization process of fibrocartilaginous entheses and may be a novel therapeutic to promote tendon‐to‐bone healing. © 2015 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 33:1142–1151, 2015.
Highlights
Tendon and ligaments attach to bone to effect joint motion and stability in response to strong and impulsive muscle forces
The objective of this study was to identify how ablating Hh signaling in Scx-expressing cells affects regional biomechanical properties, fibrocartilage maturation and collagen fiber organization in the adult murine patellar tendon
Based on our previous findings, we hypothesized that ablating Hh signaling in the patellar tendon during development would result in mature tendons exhibiting increased insertion strain and disrupted fiber organization within the mineralized fibrocartilage
Summary
Tendon and ligaments attach to bone to effect joint motion and stability in response to strong and impulsive muscle forces. Long axis of the tendon midsubstance and are organized in a hierarchical system of fibers ( referred to as “fibril bundles”) and fascicles (closely packed fibers).[5] The enthesis is the transitional structure where collagen fibrils, fibers, and fascicles of the midsubstance transition through a region of fibrocartilage before inserting into the bone.[6] The zonal insertion contains both unmineralized and mineralized fibrocartilage, characterized by a tidemark delineating these regions These two regions vary in extracellular matrix composition and organization, including mineral content and collagen types.[7,8] the orientation of collagen fibers through the enthesis is critical for efficient load transmission.[9] Following avulsion of tendon from the bone, natural healing, traditional surgical repair, and current tissue engineering strategies result in disorganized scar tissue that does not restore this integrated network of aligned collagen fibers embedded in mineralized fibrocartilage.[3,4,10,11] Such disorganized scar tissue likely explains the increased insertion strains that persist into later stages of healing.[12] Understanding the normal development and maturation of these structures may lead to novel insights into how to address the limitations of current repair techniques. Based on our previous findings, we hypothesized that ablating Hh signaling in the patellar tendon during development would result in mature tendons exhibiting increased insertion strain and disrupted fiber organization within the mineralized fibrocartilage
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