TY - JOUR
T1 - The early inflammatory response after flexor tendon healing
T2 - A gene expression and histological analysis
AU - Manning, Cionne N.
AU - Havlioglu, Necat
AU - Knutsen, Elisa
AU - Sakiyama-Elbert, Shelly E.
AU - Silva, Matthew J.
AU - Thomopoulos, Stavros
AU - Gelberman, Richard H.
PY - 2014/5
Y1 - 2014/5
N2 - Despite advances in surgical techniques over the past three decades, tendon repairs remain prone to poor clinical outcomes. Previous attempts to improve tendon healing have focused on the later stages of healing (i.e., proliferation and matrix synthesis). The early inflammatory phase of tendon healing, however, is not fully understood and its modulation during healing has not yet been studied. Therefore, the purpose of this work was to characterize the early inflammatory phase of flexor tendon healing with the goal of identifying inflammation-related targets for future treatments. Canine flexor tendons were transected and repaired using techniques identical to those used clinically. The inflammatory response was monitored for 9 days. Temporal changes in immune cell populations and gene expression of inflammation-, matrix degradation-, and extracellular matrix-related factors were examined. Gene expression patterns paralleled changes in repair-site cell populations. Of the observed changes, the most dramatic effect was a greater than 4,000-fold up-regulation in the expression of the pro-inflammatory factor IL-1β. While an inflammatory response is likely necessary for healing to occur, high levels of pro-inflammatory cytokines may result in collateral tissue damage and impaired tendon healing. These findings suggest that future tendon treatment approaches consider modulation of the inflammatory phase of healing.
AB - Despite advances in surgical techniques over the past three decades, tendon repairs remain prone to poor clinical outcomes. Previous attempts to improve tendon healing have focused on the later stages of healing (i.e., proliferation and matrix synthesis). The early inflammatory phase of tendon healing, however, is not fully understood and its modulation during healing has not yet been studied. Therefore, the purpose of this work was to characterize the early inflammatory phase of flexor tendon healing with the goal of identifying inflammation-related targets for future treatments. Canine flexor tendons were transected and repaired using techniques identical to those used clinically. The inflammatory response was monitored for 9 days. Temporal changes in immune cell populations and gene expression of inflammation-, matrix degradation-, and extracellular matrix-related factors were examined. Gene expression patterns paralleled changes in repair-site cell populations. Of the observed changes, the most dramatic effect was a greater than 4,000-fold up-regulation in the expression of the pro-inflammatory factor IL-1β. While an inflammatory response is likely necessary for healing to occur, high levels of pro-inflammatory cytokines may result in collateral tissue damage and impaired tendon healing. These findings suggest that future tendon treatment approaches consider modulation of the inflammatory phase of healing.
KW - collagen
KW - extracellular matrix
KW - inflammation
KW - intrasynovial flexor tendon
KW - matrix metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=84899455762&partnerID=8YFLogxK
U2 - 10.1002/jor.22575
DO - 10.1002/jor.22575
M3 - Article
C2 - 24464937
AN - SCOPUS:84899455762
SN - 0736-0266
VL - 32
SP - 645
EP - 652
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 5
ER -