caa a22 4500 605456666 CHVBK 20210128100219.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00167-014-3010-9 doi (NATIONALLICENCE)springer-10.1007/s00167-014-3010-9 Chemokine expression of CCL2, CCL3, CCL5 and CXCL10 during early inflammatory tendon healing precedes nerve regeneration: an immunohistochemical study in the rat [Elektronische Daten] [A. Stålman, D. Bring, P. Ackermann] Purpose: Chemokines are major promoters of repair and may regulate nerve ingrowth that is essential in tendon healing. The purpose of this study was to assess the temporal occurrence of different chemokines during Achilles tendon healing in relation to sensory nerve regeneration. Chemokine presence in tendon healing has not been studied previously. Methods: Chemokine expression, nerve regeneration, angiogenesis and inflammatory cell occurrence during healing of Achilles tendon rupture in the rat were studied by immunohistochemistry and histology including semiquantitative assessment. Markers for chemokines (CCL5, CCL2, CCL3, CXCL10), nerves (PGP-9.5) and sensory neuropeptide substance P (SP) were analysed at different time points (1day-16weeks) post-rupture. Results: In intact tendons (controls) immunoreactivity to all chemokines, PGP-9.5 and SP were confined to the tendon surroundings. After rupture, there was rapid increase in the tendon proper of the chemokines studied, all exhibiting their peak expression at week 1. Subsequently, at weeks 2-6, emerging inflammatory cells and maximum sprouting of PGP-/SP-positive nerves were observed close to newly formed blood vessels within the tendon proper, while chemokine expression already decreased. During weeks 6-8, PGP-/SP-positive nerves withdrew from the rupture site and relocated together with the chemokines in the surrounding tendon. Conclusions: Early chemokine expression in the healing tendon precedes ingrowth of new nerves, angiogenesis and emergence of inflammatory cells. The fine-tuned temporal and spatial appearance of chemokines suggests a chemoattractant role for inflammatory cell migration and possibly also a role in angiogenesis and neurogenesis. Chemokines may thus exhibit vital targets for biological modulation of tendon repair. Level of evidence: III. Springer-Verlag Berlin Heidelberg, 2014 Chemokines nationallicence Achilles tendon nationallicence Neuropeptides nationallicence Tendon rupture nationallicence Tendon repair nationallicence Nerve regeneration nationallicence Inflammation nationallicence Angiogenesis nationallicence Stålman A. Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden aut Bring D. Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden aut Ackermann P. Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden aut Knee Surgery, Sports Traumatology, Arthroscopy Springer Berlin Heidelberg 23/9(2015-09-01), 2682-2689 0942-2056 23:9<2682 2015 23 167 https://doi.org/10.1007/s00167-014-3010-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00167-014-3010-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stålman A. Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Bring D. Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Ackermann P. Integrative Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 773 0- Knee Surgery, Sports Traumatology, Arthroscopy Springer Berlin Heidelberg 23/9(2015-09-01), 2682-2689 0942-2056 23:9<2682 2015 23 167