“…Chemokines are a family of signaling proteins secreted by cells that are specific to vertebrates [ 9 ]. They can be assigned to two major subfamilies: CXC (C–X–C motif) and CC (C–C motif) chemokine [ 10 ].…”
Section: Introductionmentioning
confidence: 99%
“…They can be assigned to two major subfamilies: CXC (C–X–C motif) and CC (C–C motif) chemokine [ 10 ]. Members of these subfamilies play an important role in bone biology [ 9 ] and promote bone formation developmentally and in response to mechanical stimuli [ 11 ]. In particular, they modulate the formation of new bone and remodeling of existing bone by coordinating cellular homing, osteoblastogenesis, and osteoclastogenesis [ 10 ].…”
Section: Introductionmentioning
confidence: 99%
“…Secondly, the possibility to determine a prognostic model regarding the outcome of non-union therapy based on the expression levels of chemokines was investigated. Due to their importance in bone healing, CCL-2, CCL-3, CCL-4, CXCL-10, CCL-11, and interferon gamma (IFN-γ) [ 9 , 10 , 13 , 14 ] were included and analyzed. The hypothesis of the study was that the expression patterns of distinct cytokines correlate with bone regeneration occurring during non-union therapy and can be used to identify patients at risk at an early stage.…”
BackgroundDespite the regenerative capability of skeletal tissue fracture, non-union is common. Treatment of non-unions remains challenging, and early determination of the outcome is impossible. Chemokines play an important role in promoting the formation of new bone and remodeling existing bone. Despite their importance regarding the regulation of bone biology, the potential of chemokines as biological markers reflecting osseous regeneration is unknown.The purpose of this study was to determine (1) if serum chemokine expression levels correlate with the outcome of non-union surgery and (2) if chemokine expression analysis can be used to identify patients at risk for treatment failure.MethodsNon-union patients receiving surgical therapy in our institution between March 2012 and March 2014 were prospectively enrolled in a clinical observer study. Regular clinical and radiological follow-up was conducted for 12 months including collection of blood during the first 12 weeks. Based on the outcome, patients were declared as responders or non-responders to the therapy. To minimize biases, patients were matched (age, sex, body mass index (BMI)) and two groups of patients could be formed: responders (R, n = 10) and non-responders (NR, n = 10). Serum chemokine expression (CCL-2, CCL-3, CCL-4, CXCL-10, CCL-11, and interferon gamma (IFN-γ)) was analyzed using Luminex assays. Data was compared and correlated to the outcome.ResultsCCL-3 expression in NR was significantly higher during the course of the study compared to R (p = 0.002), and the expression pattern of CCL-4 correlated with CCL-3 in both groups (NR: p < 0.001 and r = 0.63). IFN-γ expression in NR was continuously higher than in R (p < 0.001), and utilization of CCL-3 and IFN-γ serum expression levels 2 weeks after the treatment resulted in a predictive model that had an AUC of 0.92 (CI 0.74–1.00).ConclusionSerum chemokine expression analysis over time is a valid and promising diagnostic tool. The chemokine expression pattern correlates with the outcome of the Masquelet therapy of lower limb non-unions. Utilization of the serum analysis of CCL-3 and IFN-γ 2 weeks after the treatment resulted in an early predictive value regarding the differentiation between patients that are likely to heal and those that are prone to high risk of treatment failure.Electronic supplementary materialThe online version of this article (10.1186/s13018-018-0961-4) contains supplementary material, which is available to authorized users.
“…Chemokines are a family of signaling proteins secreted by cells that are specific to vertebrates [ 9 ]. They can be assigned to two major subfamilies: CXC (C–X–C motif) and CC (C–C motif) chemokine [ 10 ].…”
Section: Introductionmentioning
confidence: 99%
“…They can be assigned to two major subfamilies: CXC (C–X–C motif) and CC (C–C motif) chemokine [ 10 ]. Members of these subfamilies play an important role in bone biology [ 9 ] and promote bone formation developmentally and in response to mechanical stimuli [ 11 ]. In particular, they modulate the formation of new bone and remodeling of existing bone by coordinating cellular homing, osteoblastogenesis, and osteoclastogenesis [ 10 ].…”
Section: Introductionmentioning
confidence: 99%
“…Secondly, the possibility to determine a prognostic model regarding the outcome of non-union therapy based on the expression levels of chemokines was investigated. Due to their importance in bone healing, CCL-2, CCL-3, CCL-4, CXCL-10, CCL-11, and interferon gamma (IFN-γ) [ 9 , 10 , 13 , 14 ] were included and analyzed. The hypothesis of the study was that the expression patterns of distinct cytokines correlate with bone regeneration occurring during non-union therapy and can be used to identify patients at risk at an early stage.…”
BackgroundDespite the regenerative capability of skeletal tissue fracture, non-union is common. Treatment of non-unions remains challenging, and early determination of the outcome is impossible. Chemokines play an important role in promoting the formation of new bone and remodeling existing bone. Despite their importance regarding the regulation of bone biology, the potential of chemokines as biological markers reflecting osseous regeneration is unknown.The purpose of this study was to determine (1) if serum chemokine expression levels correlate with the outcome of non-union surgery and (2) if chemokine expression analysis can be used to identify patients at risk for treatment failure.MethodsNon-union patients receiving surgical therapy in our institution between March 2012 and March 2014 were prospectively enrolled in a clinical observer study. Regular clinical and radiological follow-up was conducted for 12 months including collection of blood during the first 12 weeks. Based on the outcome, patients were declared as responders or non-responders to the therapy. To minimize biases, patients were matched (age, sex, body mass index (BMI)) and two groups of patients could be formed: responders (R, n = 10) and non-responders (NR, n = 10). Serum chemokine expression (CCL-2, CCL-3, CCL-4, CXCL-10, CCL-11, and interferon gamma (IFN-γ)) was analyzed using Luminex assays. Data was compared and correlated to the outcome.ResultsCCL-3 expression in NR was significantly higher during the course of the study compared to R (p = 0.002), and the expression pattern of CCL-4 correlated with CCL-3 in both groups (NR: p < 0.001 and r = 0.63). IFN-γ expression in NR was continuously higher than in R (p < 0.001), and utilization of CCL-3 and IFN-γ serum expression levels 2 weeks after the treatment resulted in a predictive model that had an AUC of 0.92 (CI 0.74–1.00).ConclusionSerum chemokine expression analysis over time is a valid and promising diagnostic tool. The chemokine expression pattern correlates with the outcome of the Masquelet therapy of lower limb non-unions. Utilization of the serum analysis of CCL-3 and IFN-γ 2 weeks after the treatment resulted in an early predictive value regarding the differentiation between patients that are likely to heal and those that are prone to high risk of treatment failure.Electronic supplementary materialThe online version of this article (10.1186/s13018-018-0961-4) contains supplementary material, which is available to authorized users.
“…A number of chemokines impact bone, having diverse effects on chondrogenesis, osteoblast differentiation, mineral opposition, fracture healing, osteoclastogenesis, and osteoclast activity, playing a role in the success and failure of implants, the bone loss in rheumatoid arthritis and the cancer-related bone loss and metastases ( 5 ). The comprehensive review by Smith et al reveals an extensive literature on environmental factors impacting bone-relevant chemokines and points out many potentially fruitful areas of research into the role of specific factors either as agents interfering with normal bone development and healing, or alternatively as potential bone therapeutic agents.…”
mentioning
confidence: 99%
“…Interestingly, Pendleton and Chandar found that exposure of preosteoblast MC3T3-E1 cells to media utilized to promote adipogenesis could be influenced by calcitriol. The wide range of effects of chemokines on bone ( 5 ) and the marked effects of vitamin D compounds in chemokine production make the involvement of chemokines in other actions of vitamin D compounds on bone an important topic meriting further investigation.…”
Dexamethasone (Dex) is known to cause significant bone growth impairment in childhood. Although previous studies have suggested roles of osteocyte apoptosis in the enhanced osteoclastic recruitment and local bone loss, whether it is so in the growing bone following Dex treatment requires to be established. The current study addressed the potential roles of chemokine CXCL12 in chondroclast/osteoclast recruitment and bone defects following Dex treatment. Significant apoptosis was observed in cultured mature ATDC5 chondrocytes and IDG-SW3 osteocytes after 48 hours of 10 À6 M Dex treatment, and CXCL12 was identified to exhibit the most prominent induction in Dex-treated cells. Conditioned medium from the treated chondrocytes/osteocytes enhanced migration of RAW264.7 osteoclast precursor cells, which was significantly inhibited by the presence of the anti-CXCL12 neutralizing antibody. To investigate the roles of the induced CXCL12 in bone defects caused by Dex treatment, young rats were orally gavaged daily with saline or Dex at 1 mg/kg/day for 2 weeks, and received an intraperitoneal injection of anti-CXCL12 antibody or control IgG (1 mg/kg, three times per week). Aside from oxidative stress induction systemically, Dex treatment caused reductions in growth plate thickness, primary spongiosa height, and metaphysis trabecular bone volume, which are associated with induced chondrocyte/ osteocyte apoptosis and enhanced chondroclast/osteoclast recruitment and osteoclastogenic differentiation potential. CXCL12 was induced in apoptotic growth plate chondrocytes and metaphyseal bone osteocytes. Anti-CXCL12 antibody supplementation considerably attenuated Dex-induced chondroclast/osteoclast recruitment and loss of growth plate cartilage and trabecular bone. CXCL12 neutralization did not affect bone marrow osteogenic potential, adiposity, and microvasculature. Thus, CXCL12 was identified as a potential molecular linker between Dex-induced skeletal cell apoptosis and chondroclastic/osteoclastic recruitment, as well as growth plate cartilage/bone loss, revealing a therapeutic potential of CXCL12 functional blockade in preventing bone growth defects during/after Dex treatment. CHEMOKINE CXCL12 IN DEX THERAPY-INDUCED BONE GROWTH DEFECTS 311 54. Ellies DL, Viviano B, McCarthy J, et al. Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006;21(11):1738-49. 55. Hosogane N, Huang Z, Rawlins BA, et al. Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. Int J Biochem
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