Only the co ‐transcriptional activity of β‐catenin is required for the local regulatory effects in hypertrophic chondrocytes on developmental bone modeling

ABSTRACTIn hypertrophic chondrocytes, β-catenin has two roles. First, it locally suppresses the differentiation of osteoclasts at the chondro-osseous junction by maintaining the pro-osteoclastic factor RANKL at low levels. Secondly, it promotes the differentiation of osteoblast-precursors from chondrocytes. Yet, β-catenin is a dual-fu nction protein, which can either participate in cell–cell adherens junctions or serve as a transcriptional co-activator in canonical Wnt signaling interacting with TCF/LEF transcription factors. Hence, whenever studying tissue-specific requirements of β-catenin using a conventional conditional kn ock-out approach, the functional mechanisms underlying the defects in the conditional mutants remain ambiguous. To decipher mechanistically which of the two molecular functions of β-catenin is required in hypertrophic chondrocytes, we used different approaches. We analyzed the long bones of newborn mice carrying either the null-alleles ofLef1 orTcf7, or mice, in whichTcf7l2 was conditionally deleted in the hypertrophic chondrocytes, as well as double-mutants forLef1 andTcf7l2, andTcf7 andTcf7l2. Furthermore, we analyzedCtnnb1 mutant newborns expressing a signaling-defective allele that retains the cell adhesion function in hypertrophic chondrocytes. None of the analyzed Tcf/Lef single or double-mutants recapitulated the previously published phenotype upon loss of β-catenin in hypertrophic chondrocytes. However, using this particularCtnnb1 allele,...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
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