Interleukin-6 inhibits bone formation in vitro

Hughes, Francis J.; Howells, Gareth L.

doi:10.1016/s0169-6009(08)80117-1

Cited by 133 publications

(63 citation statements)

References 24 publications

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“…[15][16][17] It was originally described as a factor with a crucial role in the immune response, but subsequently IL-6 was also implicated in the inflammatory process, 18 viral infection, 19 autoimmunity, 20 development, 21 malignant cell growth, 17 and bone metabolism. 22 However, the possible role of IL-6 in the regulation of blood pressure and sodium-water balance has not been investigated extensively.…”

Section: Discussionmentioning

confidence: 99%

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women

et al. 1999

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Genes that can be implicated in hypertension in experimental animals are plausible candidates in the pathogenesis of human hypertension. A recent genome-wide search for quantitative-trait loci (QTL) in hypertensive rats revealed a strong correlation between the interleukin-6 (IL-6) locus on rat chromosome 4 and systolic, diastolic, and mean arterial pressure in this mammalian species. To investigate a possible association between genetic variations of the IL-6 gene and hypertension in humans, we identified two novel single-nucleotide sequence variations, a C/G substitution at −634 in the promoter region and a G/A substitution at 4391 in a 3 ′ non-coding portion of exon 5, and a previous reported sequence variant, an A/T variation in the composition of the A n T n tract around −447 in the promoter region ( Fishman D et al. J Clin Invest 1998; 102: 1369-1376, within a test population of 96 Japanese subjects. Allelic associations involving these variations were analyzed in 150 hypertensive and 143 normotensive Japanese women. The distribution of alleles of the three polymorphisms, as well as a dinucleotide repeat present at the IL-6 locus, was similar in the two groups. Therefore, the IL-6 gene appears to play a minimal role in the genetic etiology of essential hypertension in Japanese women.

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Section: Discussionmentioning

confidence: 99%

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women

et al. 1999

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“…Bone IL-6 is known to induce osteoblast formation (Lowik et al, 1989) and bone resorption (Ishimi et al, 1990). Recently, it has been reported that IL-6 inhibits bone formation in vitro (Hughes & Howells, 1993). In culture, IL-6 is produced by bone marrow-derived stromal and osteoblastic cells from rat, murine and human sources (Lowik et al, 1989;Feyen et al, 1989;Ishimi et al, 1990;Girasole et al, 1992;Chaudhary et al, 1992;Rahman et al, 1992) and its release is stimulated by PTH, 1,25(OH)2D3, bradykinin, IL-1 and TNF-a (Lowik et al, 1989;Rahman et al, 1992;Chaudhary et al, 1992;Passeri et al, 1993).…”

Section: Male Reproductive Tractmentioning

confidence: 99%

Interleukin‐6 an endocrine cytokine

Jones

1994

Clinical Endocrinology

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“…[12][13][14] There is a substantial body of research that suggest that IL-6 exerts effects on bone homeostasis and repair. IL-6 stimulates production of RANK ligand by osteoblasts which, in turn, catalyzes the formation of osteoclasts from peripheral blood monocytes.15 It was shown to induce differentiation of pre-osteoblasts, [16][17][18] inhibit nodule formation in bone culture, 19 and induce cathepsin B production by osteoblasts.20 During distraction osteogenesis, IL-6 is produced by osteoblasts, hemopoietic cells, and cells associated with the lengthening callus. 21 Murine models of fracture healing have shown elevations in IL-6 during intramembranous callus remodeling 22 as well as secondary bone remodeling associated with endochondral ossification.…”

mentioning

confidence: 99%

“…15 It was shown to induce differentiation of pre-osteoblasts, [16][17][18] inhibit nodule formation in bone culture, 19 and induce cathepsin B production by osteoblasts.…”

mentioning

confidence: 99%

“…IL-6 stimulates production of RANK ligand by osteoblasts which, in turn, catalyzes the formation of osteoclasts from peripheral blood monocytes. 15 It was shown to induce differentiation of pre-osteoblasts, [16][17][18] inhibit nodule formation in bone culture, 19 and induce cathepsin B production by osteoblasts. 20 During distraction osteogenesis, IL-6 is produced by osteoblasts, hemopoietic cells, and cells associated with the lengthening callus.…”

mentioning

confidence: 99%

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Effects of Interleukin‐6 Ablation on Fracture Healing in Mice

Wallace

Cooney

Englund

et al. 2011

Journal Orthopaedic Research

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This study examined the impact of an interleukin-6 (IL-6) knockout on fracture healing in terms of histological and biomechanical responses. Following IACUC approval, tibial fractures were produced in 4-to 6-week-old IL-6 knockouts (n ¼ 35) and wild-type mice (n ¼ 36) and harvested along with contralateral limbs at 2 and 6 weeks postsurgery. Histology quantified stage of healing, lymphocyte infiltration, TRAPþ cells, and osteocalcin deposition. Bend testing established maximum load and stiffness. Based on normality assessments, Mann-Whitney U or independent t-tests were used for data analysis using a p-value threshold of 0.05. Stage of healing, lymphocyte infiltration, and osteocalcin deposition were similar for all time points (p ! 0.243). TRAPþ cell counts were reduced approximately 10-fold in the knockout at 2 weeks (p ¼ 0.015) but were similar at 6 weeks (p ¼ 0.689). Force-to-failure in knockouts was approximately 40% that of wild-type mice at 2 weeks (p ¼ 0.040) but similar at 6 weeks (p ¼ 0.735). Knockout bone was about 25% less stiff at 2 weeks but approximately 60% stiffer at 6 weeks (p ! 0.110). The absence of IL-6 during early fracture healing significantly reduced osteoclastogenesis and impaired callus strength. By 6 weeks, most histological and biomechanical parameters were similar to fractures in wild-type bone. Keywords: cytokines; interleukin-6; fracture healing Inflammation is a key component to both wound and bony healing responses. Leukocytosis is a part of this phenomenom and is integral to fracture healing.1-3 In particular, neutrophil infiltration is apparently allied with establishing chondrogenesis, a sentinel component of endochondral ossification. 4Cytokines are also involved in regulating the healing response. IL-1 plays a prominent role in the early response to injury, 5-7 exerting both proliferative [7][8][9][10] and catabolic effects. 11 It also stimulates the expression of IL-6 by osteoblasts. [12][13][14] There is a substantial body of research that suggest that IL-6 exerts effects on bone homeostasis and repair. IL-6 stimulates production of RANK ligand by osteoblasts which, in turn, catalyzes the formation of osteoclasts from peripheral blood monocytes.15 It was shown to induce differentiation of pre-osteoblasts, [16][17][18] inhibit nodule formation in bone culture, 19 and induce cathepsin B production by osteoblasts.20 During distraction osteogenesis, IL-6 is produced by osteoblasts, hemopoietic cells, and cells associated with the lengthening callus. 21 Murine models of fracture healing have shown elevations in IL-6 during intramembranous callus remodeling 22 as well as secondary bone remodeling associated with endochondral ossification. 23 Recently, Yang et al. 24 provided insight into the effects of IL-6 on fracture healing, noting an impairment of osteoclastogenesis. Similarly, Axmann et al. 25 showed that abrogating IL-6 receptor function also reduced osteoclast counts in a model of inflammatory (RA) bone erosion.Given the importance of the inflammatory response ...

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Interleukin-6 inhibits bone formation in vitro

Cited by 133 publications

References 24 publications

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women

Interleukin‐6 an endocrine cytokine

Effects of Interleukin‐6 Ablation on Fracture Healing in Mice

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