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Updated: Jul 8, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
The protein tyrosine phosphatase Rptpzeta is expressed in differentiated osteoblasts and affects bone formation in
T Schinke1, M Gebauer, A F Schilling
1Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg Eppendorf, Hamburg 20246, Germany.
Abstract:
Tyrosine phosphorylation of intracellular substrates is one mechanism to regulate cellular proliferation and differentiation. Protein tyrosine phosphatases (PTPs) act by dephosphorylation of substrates and thereby counteract the activity of tyrosine kinases. Few PTPs have been suggested to play a role in bone remodeling, one of them being Rptpzeta, since it has been shown to be suppressed by pleiotrophin, a heparin-binding molecule affecting bone formation, when over-expressed in transgenic mice. In a genome-wide expression analysis approach we found that Ptprz1, the gene encoding Rptpzeta, is strongly induced upon terminal differentiation of murine primary calvarial osteoblasts. Using RT-PCR and Western Blotting we further demonstrated that differentiated osteoblasts, in contrast to neuronal cells, specifically express the short transmembrane isoform of Rptpzeta. To uncover a potential role of Rptpzeta in bone remodeling we next analyzed the skeletal phenotype of a Rptpzeta-deficient mouse model using non-decalcified histology and histomorphometry. Compared to wildtype littermates, the Rptpzeta-deficient mice display a decreased trabecular bone volume at the age of 50 weeks, caused by a reduced bone formation rate. Likewise, Rptpzeta-deficient calvarial osteoblasts analyzed ex vivo display decreased expression of osteoblast markers, indicating a cell-autonomous defect. This was confirmed by the finding that Rptpzeta-deficient osteoblasts had a diminished potential to form osteocyte-like cellular extensions on Matrigel-coated surfaces. Taken together, these data provide the first evidence for a physiological role of Rptpzeta in bone remodeling, and thus identify Rptpzeta as the first PTP regulating bone formation in vivo.
Insights
Protein tyrosine phosphatase zeta (Rptpzeta) is crucial for bone remodeling. Mice lacking Rptpzeta show reduced bone volume and impaired osteoblast function, indicating its role in bone formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Bone Biology
Background:
- Protein tyrosine phosphatases (PTPs) regulate cellular processes by counteracting tyrosine kinases.
- Rptpzeta, a PTP, has been implicated in bone remodeling, with its expression affected by pleiotrophin.
- The specific role of Rptpzeta in bone formation remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of Rptpzeta in bone remodeling.
- To determine the expression pattern of Rptpzeta in osteoblasts.
- To analyze the skeletal phenotype of Rptpzeta-deficient mice.
Main Methods:
- Genome-wide expression analysis to identify Ptprz1 induction in osteoblasts.
- RT-PCR and Western Blotting to confirm Rptpzeta isoform expression.
- Histomorphometry and histology of Rptpzeta-deficient mouse models.
- Ex vivo analysis of Rptpzeta-deficient osteoblasts.
Main Results:
- Ptprz1 (Rptpzeta gene) is strongly induced during osteoblast differentiation.
- Differentiated osteoblasts specifically express the short transmembrane isoform of Rptpzeta.
- Rptpzeta-deficient mice exhibit decreased trabecular bone volume and reduced bone formation rate.
- Rptpzeta-deficient osteoblasts show reduced expression of osteoblast markers and impaired osteocyte-like extension formation.
Conclusions:
- Rptpzeta plays a significant physiological role in bone remodeling.
- Rptpzeta is essential for regulating bone formation in vivo.
- This study identifies Rptpzeta as the first PTP to directly regulate bone formation.
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