Potential Role of Chemokines in Fracture Repair

Edderkaoui, Bouchra

doi:10.3389/fendo.2017.00039

Cited by 50 publications

(53 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of CCL3 in myeloma‐induced bone disease was investigated by Vallet et al They found osteocalcin expression downregulated and osteoblast mineralization inhibited by CCL3 (Vallet et al, ). This observation is confirmed by other authors, who report CCL3 to impair mineralization in fracture healing and high serum levels of CCL3 to be associated with delayed fracture healing (Edderkaoui, ; Fu et al, ).…”

Section: Discussionsupporting

confidence: 83%

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

et al. 2019

View full text Add to dashboard Cite

The Masquelet technique for the treatment of large bone defects is a two‐stage procedure based on an induced membrane. The size of a scaffold is reported to be a critical factor for bone healing response. We therefore aimed to investigate the influence of the granule size of a bone graft substitute on bone marrow derived mononuclear cells (BMC) supported bone healing in combination with the induced membrane. We compared three different sizes of Herafill® granules (Heraeus Medical GmbH, Wehrheim) with or without BMC in vivo in a rat femoral critical size defect. A 10 mm defect was made in 126 rats and a membrane induced by a PMMA‐spacer. After 3 weeks, the spacer was taken out and membrane filled with different granule sizes. After 8 weeks femurs were taken for radiological, biomechanical, histological, and immunohistochemical analysis. Further, whole blood of the rat was incubated with granules and expression of 29 peptide mediators was assessed. Smallest granules showed significantly improved bone healing compared to larger granules, which however did not lead to an increased biomechanical stability in the defect zone. Small granules lead to an increased accumulation of macrophages in situ which could be assigned to the inflammatory subtype M1 by majority. Increased release of chemotactic respectively proangiogenic active factors in vitro compared to syngenic bone and beta‐TCP was observed. Granule size of the bone graft substitute Herafill® has significant impact on bone healing of a critical size defect in combination with Masquelet's technique in terms of bone formation and inflammatory potential.

show abstract

Section: Discussionsupporting

confidence: 83%

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

et al. 2019

View full text Add to dashboard Cite

show abstract

“…RNA microarrays of the fracture site among the group that received NSAID during the active time revealed an upregulation of genes signalling cytokines associated with the polarization of macrophage cells from M1 phenotype to M2 such as Retnla, FIZZ1 and IL-4R1 during bone healing 47 . This group also showed expression of genes www.nature.com/scientificreports www.nature.com/scientificreports/ associated with the recruitment of mesenchymal stem cells and the initiation of the angiogenesis process such as CXCR4 and CCL12 44 (Table S4). In addition, the group that received NSAID during the active phase demonstrated a downregulation of transcripts associated with the expression of pro-inflammatory cytokines including Stat1, IL-9, IL-6ra, and IL-18 48,49 .…”

Section: Discussionmentioning

confidence: 94%

“…Our gene ontology analysis of the differentially expressed genes suggested that the timing of NSAID administration after bone fracture affected several signalling pathways such as: the inflammation mediated pathway, the interleukin, T-cell and B-cell activation signalling pathways, and the EGFR signaling pathway. Studies have demonstrated the effect of these pathways [44][45][46] on regulating cytokine signaling and the immune response.…”

Section: Discussionmentioning

confidence: 99%

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

Al-Waeli

Nicolau

Stone

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment. open Scientific RepoRtS | (2020) 10:468 | https://doi.org/10.1038/s41598-019-57215-y www.nature.com/scientificreports www.nature.com/scientificreports/ and Table S2). For instance, macrophage activity, leukocyte recruitment, and pro-inflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-12 (IL-12) increase at the beginning of daily activity. During this phase, the levels of Tol-Like Receptors TLR9 and TLR4 also increase, leading to the upregulation of CCL2, CXCL1, CCL5, and subsequent leukocyte recruitment and potential tissue damage in injured sites 12-15 ( Fig. 1). By contrast, anti-inflammatory mediators and other growth or angiogenesis factors, such as the vascular endothelial growth factor (VEGF), peak during the resting phase 13,16,17 ( Fig. 1 and Table S2).The circadian rhythm affects many aspects of connective tissue metabolism 18 . A 24-hour oscillation occurs in bone tissue during growth 19 , formation, resorption 20,21 , and in the endochondral ossification during bone fracture healing 21 . Bone formation occurs during the resting period, and resorption occurs mostly during the active period 21 . Experimental studies in rodents and humans reveal that the disruption of sleep and circadian rhythm impairs bone formation 22 . All bone cells such as osteoblasts, osteoclasts, and chondrocytes express clock genes, such as Per or Cry, that influence bone volume regulation 23,24 . Cry2 influences the osteoclastic activity and Per2 regulates osteoblast activity 25 . The circadian clock also affects pain, with sensitivity peaking during the active phase 26 . Part of the pain response oscillation could b...

show abstract

“…Under inflammatory conditions, EGF is a potent inducer of angiogenesis and bone growth by significantly upregulating secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2), an osteoinductive growth factor (50). MCP-1 has also been shown to be a key cytokine involved in both inflammation and bone remodeling, in particular with processes that include neutrophil migration, macrophage infiltration, and angiogenesis (51). Similarly, LIX and RANTES are known for their chemotactic and pro-inflammatory properties that have both been associated with the necessary inflammatory phase during the fracture repair process (52,53).…”

Section: Prevention Of Tcr and T Cell Activation Inhibits One Of The mentioning

confidence: 99%

Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection

Vantucci

Ahn

Schenker

et al. 2020

Preprint

View full text Add to dashboard Cite

Orthopedic biomaterial-associated infections remain a large clinical challenge, particularly with open fractures and segmental bone loss. Invasion and colonization of bacteria within immuneprivileged canalicular networks of the bone can lead to local, indolent infections that can persist for years without symptoms before eventual catastrophic hardware failure. Host immunity is essential for bacterial clearance and an appropriate healing response, and recent evidence has suggested an association between orthopedic trauma and systemic immune dysregulation and immunosuppression. However, the impact of a local infection on this systemic immune response and subsequent effects on the local response is poorly understood and has not been a major focus for addressing orthopedic injuries and infections. Therefore, this study utilized a model of orthopedic biomaterial-associated infection to investigate the effects of infection on the longterm immune response. Here, despite persistence of a local, indolent infection lacking outward symptoms, there was still evidence of long-term immune dysregulation with systemic increases in MDSCs and decreases in T cells compared to non-infected trauma. Further, the trauma only group exhibited a regulated and coordinated systemic cytokine response, which was not present in the infected trauma group. Locally, the infection group had attenuated macrophage infiltration in the local soft tissue compared to the non-infected group. Our results demonstrate widespread impacts of a localized orthopedic infection on the systemic and local immune responses.Characterization of the immune response to orthopedic biomaterial-associated infection may identify key targets for immunotherapies that could optimize both regenerative and antibiotic interventions, ultimately improving outcomes for these patients.

show abstract

Potential Role of Chemokines in Fracture Repair

Cited by 50 publications

References 99 publications

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery

Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection

Contact Info

Product

Resources

About