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- Emons, J, et al.
(författare)
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Mechanisms of growth plate maturation and epiphyseal fusion
- 2011
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 75:6, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal growth occurs within the long bones at the growth plate. During childhood, the growth plate matures, its total width decreases and eventually it disappears at the end of puberty with complete replacement by bone along with cessation of longitudinal growth. The exact mechanism of epiphyseal fusion is still not completely understood and experimental studies are complicated by the fact that there is a species difference between humans and rabbits that do fuse their growth plates and rodents that do not. This mini review summarizes hypotheses and theories postulated in the literature regarding growth plate maturation and epiphyseal fusion. Growth factors, local regulators and hormones involved in growth plate maturation are described as well as four postulated hypotheses and theories regarding the final steps in epiphyseal fusion: apoptosis, autophagy, transdifferentiation and hypoxia. A better insight into the mechanisms of epiphyseal fusion may ultimately help to develop new strategies for the treatment of cartilage and growth disorders.
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- Huang, X., et al.
(författare)
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Dickkopf-related protein 1 and gremlin 1 show different response than frizzled-related protein in human synovial fluid following knee injury and in patients with osteoarthritis
- 2018
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:6, s. 834-843
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the involvement of the wingless-type MMTV integration site (WNT) and bone morphogenetic protein (BMP) antagonists dickkopf-related protein 1 (DKK1), frizzled-related protein (FRZB) and gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). Design: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of nine knee healthy reference subjects, patients with recent (0–77 days, n = 158) or old (1–37 years, n = 50) knee injuries, and OA (n = 22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples. Statistical analysis was by Kendall's tau (τ) correlation, Mann–Whitney U test, and linear regression analysis. Results: Compared to references, median concentration of GREM1 (but not DKK1 and FRZB) was elevated 1.5-fold immediately after injury, and FRZB was reduced 1000-folds in OA. All three antagonists decreased with increasing time after injury as well as with increasing age, but the temporal change after injury was less accentuated for FRZB (peaked 8–22 days after injury) compared to that of DKK1 and GREM1 (peaked immediately after injury). In the recent injury group, there was a correlation between GREM1 and DKK1 (τ = 0.172); FRZB concentrations correlated with concentrations of cartilage biomarkers (τ between 0.257 and 0.369), while DKK1 and GREM1 were inversely correlated (τ between −0.177 and −0.217) with these markers. Conclusions: Our results indicate separate roles for the antagonists, where DKK1 and GREM1 had similarities in response to injury and in OA, with a different response for FRZB.
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- van Bezooijen, Rutger L., et al.
(författare)
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Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation
- 2007
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Ingår i: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 22:1, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family of glycoproteins of which many members have been reported to antagonize BMP activity. Sclerostin has been shown to inhibit BMP-stimulated bone formation, but its mechanism of action seems to be different from classical BMP antagonists. In this study, we investigated the mechanism by which sclerostin inhibits BMP-stimulated bone formation. Materials and Methods: DNA electroporation of calf muscle of mice using expression plasmids for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced bone formation in vivo. Transcriptional profiling using microarrays of osteoblastic cells treated with BMP in the absence or presence of sclerostin was used to find specific growth factor signaling pathways affected by sclerostin. The affected pathways were further studied using growth factor-specific reporter constructs. Results: BMP-induced ectopic bone formation in calf muscle of mice was prevented by co-expression of sclerostin in vivo. Transcriptional profiling analysis of osteoblastic cultures indicated that sclerostin specifically affects BMP and Wnt signaling out of many other growth signaling pathways. Sclerostin, however, did not inhibit stimulation of direct BMP target genes. Furthermore, we did not obtain any evidence for sclerostin acting as a direct BMP antagonist using a BMP-specific reporter construct. In contrast, sclerostin shared many characteristics with the Wnt antagonist dickkopf-1 in antagonizing BMP-stimulated bone formation and BMP- and Wnt-induced Wnt reporter construct activation. Conclusions: Sclerostin inhibits BMP-stimulated bone formation but does not affect BMP signaling. Instead, it antagonizes Wnt signaling in osteoblastic cells. High bone mass in sclerosteosis and van Buchem disease may, therefore, result from increased Wnt signaling.
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