β-catenin activity in late hypertrophic chondrocytes locally orchestrates osteoblastogenesis and osteoclastogenesis

Houben A, Kostanova-Poliakova D, Weissenboeck M, Graf J, Teufel S, Mark K, Hartmann C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Development Company of Biologists

Book Volume: 143

Pages Range: 3826-3838

Journal Issue: 20

DOI: 10.1242/dev.137489

Abstract

Trabecular bone formation is the last step in endochondral ossification. This remodeling process of cartilage into bone involves blood vessel invasion and removal of hypertrophic chondrocytes (HTCs) by chondroclasts and osteoclasts. Periosteal- and chondrocyte-derived osteoprogenitors utilize the leftover mineralized HTC matrix as a scaffold for primary spongiosa formation. Here, we show genetically that ?-catenin (encoded by Ctnnb1), a key component of the canonical Wnt pathway, orchestrates this remodeling process at multiple levels. Conditional inactivation or stabilization of ?-catenin in HTCs by a Col10a1-Cre line locally modulated osteoclastogenesis by altering the Rankl:Opg ratio in HTCs. Lack of ?-catenin resulted in a severe decrease of trabecular bone in the embryonic long bones. Gain of ?-catenin activity interfered with removal of late HTCs and bone marrow formation, leading to a continuous mineralized hypertrophic core in the embryo and resulting in an osteopetrotic-like phenotype in adult mice. Furthermore, ?-catenin activity in late HTCs is required for chondrocyte-derived osteoblastogenesis at the chondro-osseous junction. The latter contributes to the severe trabecular bone phenotype in mutants lacking ?-catenin activity in HTCs.

Authors with CRIS profile

Klaus von der Mark Medizinische Fakultät

Additional Organisation(s)

Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Forschungsinstitut für Molekulare Pathologie / Research Institute of Molecular Pathology (IMP) AT Austria (AT)

How to cite

APA:

Houben, A., Kostanova-Poliakova, D., Weissenboeck, M., Graf, J., Teufel, S., Mark, K., & Hartmann, C. (2016). β-catenin activity in late hypertrophic chondrocytes locally orchestrates osteoblastogenesis and osteoclastogenesis. Development, 143(20), 3826-3838. https://dx.doi.org/10.1242/dev.137489

MLA:

Houben, Astrid, et al. "β-catenin activity in late hypertrophic chondrocytes locally orchestrates osteoblastogenesis and osteoclastogenesis." Development 143.20 (2016): 3826-3838.

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