title: CaMKII Signaling Stimulates Mef2c ActivityIn Vitrobut Only Minimally Affects Murine Long Bone Developmentin vivo.
abstract: The long bones of vertebrate limbs form by endochondral ossification, whereby mesenchymal cells differentiate into chondrogenic progenitors, which then differentiate into chondrocytes. Chondrocytes undergo further differentiation from proliferating to prehypertrophic, and finally to hypertrophic chondrocytes. Several signaling pathways and transcription factors regulate this process. Previously, we and others have shown in chicken that overexpression of an activated form of Calcium/calmodulin-dependent kinase II (CaMKII) results in ectopic chondrocyte maturation. Here, we show that this is not the case in the mouse. Although,in vitroMef2c activity was upregulated by about 55-fold in response to expression of an activated form of CaMKII (DACaMKII), transgenic mice that expressed a dominant-active form of CaMKII under the control of the Col2a1 regulatory elements display only a very transient and mild phenotype. Here, only the onset of chondrocyte hypertrophy at E12.5 is accelerated. It is also this early step in chondrocyte differentiation that is temporarily delayed around E13.5 in transgenic mice expressing the peptide inhibitor CaM-KIIN from rat (rKIIN) under the control of the Col2a1 regulatory elements. Yet, ultimately DACaMKII, as well as rKIIN transgenic mice are born with completely normal skeletal elements with regard to their length and growth plate organization. Hence, ourin vivoanalysis suggests that CaMKII signaling plays a minor role in chondrocyte maturation in mice.
authors.affiliation: Department Bone and Skeletal Research, Medical Faculty of the University of Münster (WWU), Institute of Experimental Musculoskeletal Medicine Münster, Germany.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Amara
authors.affiliation: Department Bone and Skeletal Research, Medical Faculty of the University of Münster (WWU), Institute of Experimental Musculoskeletal Medicine Münster, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Fabritius
authors.affiliation: Department Bone and Skeletal Research, Medical Faculty of the University of Münster (WWU), Institute of Experimental Musculoskeletal Medicine Münster, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Houben
authors.affiliation: Department Bone and Skeletal Research, Medical Faculty of the University of Münster (WWU), Institute of Experimental Musculoskeletal Medicine Münster, Germany.
authors.forename: Lena I
authors.initials: LI
authors.lastname: Wolff
authors.affiliation: Department Bone and Skeletal Research, Medical Faculty of the University of Münster (WWU), Institute of Experimental Musculoskeletal Medicine Münster, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
keywords: CaMKII; Mef2c; chondrocyte maturation; hypertrophy; mouse model; peptide inhibitor