title: Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing.
abstract: Acute and chronic tendinopathies remain clinically challenging and tendons are predisposed to degeneration or injury with age. Despite the high prevalence of tendon disease in the elderly, our current understanding of the mechanisms underlying the age-dependent deterioration of tendon function remains very limited. Here, we show that Secreted protein acidic and rich in cysteine (Sparc) expression significantly decreases in healthy-aged mouse Achilles tendons. Loss of Sparc results in tendon collagen fibrillogenesis defects and Sparc-/- tendons are less able to withstand force in comparison with their respective wild type counterparts. On the cellular level, Sparc-null and healthy-aged tendon-derived cells exhibited a more contracted phenotype and an altered actin cytoskeleton. Additionally, an elevated expression of the adipogenic marker genes PPARγ and Cebpα with a concomitant increase in lipid deposits in aged and Sparc-/- tendons was observed. In summary, we propose that Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties favors lipid accretion in tendons.
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Renate
authors: R
authors: Gehwolf
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Andrea
authors: A
authors: Wagner
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Christine
authors: C
authors: Lehner
authors: Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, USA.
authors: Amy D
authors: AD
authors: Bradshaw
authors: Experimental and Clinical Cell Therapy Institute, Paracelsus Medical University Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.
authors: Cornelia
authors: C
authors: Scharler
authors: Institute of Biomechanics, Graz University of Technology, Graz, Austria.
authors: Justyna A
authors: JA
authors: Niestrawska
authors: Institute of Biomechanics, Graz University of Technology, Graz, Austria.
authors: Gerhard A
authors: GA
authors: Holzapfel
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Hans-Christian
authors: HC
authors: Bauer
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Herbert
authors: H
authors: Tempfer
authors: Institute of Tendon and Bone Regeneration, Paracelsus Medical University - Spinal Cord Injury &Tissue Regeneration Center Salzburg, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors: Andreas
authors: A
authors: Traweger
mesh_terms: D050156:Adipogenesis; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D048430:Cell Shape; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D058685:Genetic Pleiotropy; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D015676:Osteonectin / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D013234:Stem Cells / Q000166:cytology; D013710:Tendons / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D015415:Biomarkers; D015676:Osteonectin