Reduced β-catenin expression affects patterning of bone primordia, but not bone maturation.

Pflug, Tobias; Huynh-Do, Uyen; Rudloff, Stefan (2017). Reduced β-catenin expression affects patterning of bone primordia, but not bone maturation. Biology open BiO, 6(5), pp. 582-588. Company of Biologists 10.1242/bio.023572

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Wnt/β-catenin signaling is involved in patterning of bone primordia, but also plays an important role in the differentiation of chondrocytes and osteoblasts. During these processes the level of β-catenin must be tightly regulated. Excess β-catenin leads to conditions with increased bone mass, whereas loss of β-catenin is associated with osteoporosis or, in extreme cases, the absence of limbs. In this study, we examined skeletogenesis in mice, which retain only 25% of β-catenin. These embryos showed severe morphological abnormalities of which the lack of hindlimbs and misshaped front paws were the most striking. Surprisingly however, calcification of bone primordia occurred normally. Moreover, the Wnt-dependent regulatory network of transcription factors driving the differentiation of cartilage and bone, as well as the expression of extracellular matrix components, were preserved. These findings show that 25% β-catenin is insufficient for the correct patterning of bone primordia, but sufficient for their mineralization. Our approach helps to identify bone morphogenetic processes that can proceed normally even at low β-catenin levels, in contrast to those that require high β-catenin dosages. This information could be exploited to improve the treatment of bone diseases by fine-tuning the individual β-catenin dosage requirements.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Huynh-Do, Uyen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2046-6390

Publisher:

Company of Biologists

Language:

English

Submitter:

Uyen Huynh-Do

Date Deposited:

01 Oct 2019 13:16

Last Modified:

25 Oct 2019 01:16

Publisher DOI:

10.1242/bio.023572

PubMed ID:

28347990

Uncontrolled Keywords:

Bone development Canonical Wnt signaling Limb patterning β-catenin dosage

BORIS DOI:

10.7892/boris.131759

URI:

https://boris.unibe.ch/id/eprint/131759

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