Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate
Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate
Filamin B (FlnB) is an actin-binding protein thought to transduce signals from various membrane receptors and intracellular proteins onto the actin cytoskeleton. Formin1 (Fmn1) is an actin-nucleating protein, implicated in actin assembly and intracellular signaling. Human mutations in FLNB cause several skeletal disorders associated with dwarfism and early bone fusion. Mouse mutations in Fmn1 cause aberrant fusion of carpal digits. We report here that FlnB and Fmn1 physically interact, are co-expressed in chondrocytes in the growth plate and share overlapping expression in the cell cytoplasm and nucleus. Loss of FlnB leads to a dramatic decrease in Fmn1 expression at the hypertrophic-to-ossification border. Loss of Fmn1-FlnB in mice leads to a more severe reduction in body size, weight and growth plate length, than observed in mice following knockout of either gene alone. Shortening of the long bone is associated with a decrease in chondrocyte proliferation and an overall delay in ossification in the double-knockout mice. In contrast to FlnB null, Fmn1 loss results in a decrease in the width of the prehypertrophic zone. Loss of both proteins, however, causes an overall decrease in the width of the proliferation zone and an increase in the differentiated hypertrophic zone. The current findings suggest that Fmn1 and FlnB have shared and independent functions. FlnB loss promotes prehypertrophic differentiation whereas Fmn1 leads to a delay. Both proteins, however, regulate chondrocyte proliferation, and FlnB may regulate Fmn1 function at the hypertrophic-to-ossification border, thereby explaining the overall delay in ossification.
- Central European Institute of Technology Czech Republic
- Beth Israel Deaconess Medical Center Harvard Medical School United States
- Masaryk University Czech Republic
- Beth Israel Deaconess Medical Center United States
- Albany Medical Center Hospital United States
Fetal Proteins, Mice, Knockout, Filamins, Microfilament Proteins, Formins, Nuclear Proteins, Cell Differentiation, Hypertrophy, Protein Transport, Calcification, Physiologic, Chondrocytes, Animals, Humans, Growth Plate, Cell Proliferation, Protein Binding, Receptor, Parathyroid Hormone, Type 1
Fetal Proteins, Mice, Knockout, Filamins, Microfilament Proteins, Formins, Nuclear Proteins, Cell Differentiation, Hypertrophy, Protein Transport, Calcification, Physiologic, Chondrocytes, Animals, Humans, Growth Plate, Cell Proliferation, Protein Binding, Receptor, Parathyroid Hormone, Type 1
39 Research products, page 1 of 4
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).30 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
