The Journal of biological chemistryApr 29, 2026

A genome-wide CRISPR screen finds Clip2 as a new controller of bone cell development and shape

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated May 1, 2026

Abstract

CD61 expression increases during osteocyte maturation, indicating its potential as a marker for this process.

Surface CD61 levels rise as osteocytes mature, correlating with higher expression of osteocyte marker genes.
A genome-wide CRISPR-interference screen identified Clip2 as essential for maintaining CD61 expression.
Inhibition of Clip2 led to decreased CD61 expression and lower levels of osteocyte-specific genes Dmp1 and Sost.
Impairments in dendrite morphology were observed following Clip2 inhibition in vitro.
These findings suggest a link between the microtubule cytoskeleton and osteocyte differentiation and function.

Simplified

Osteocytes play critical roles in bone, making them attractive targets for therapeutics to improve bone mass and strength. The genes driving osteocyte maturation and function are not fully understood. Here we aimed to identify novel genes responsible for osteocyte differentiation and dendrite development by performing a genome-wide CRISPR-interference (CRISPRi) screen in the Ocy454 osteocyte-like cell line. We identify CD61 (integrin β3) as a marker of osteocyte maturation: surface CD61 expression increases during osteocyte maturation, and CD61cells express higher levels of osteocyte marker genes. We then developed a flow cytometry-based assay to quantify surface CD61 protein levels as a phenotypic endpoint for functional genomic screening. In a genome-wide screen, we identified Clip2, which encodes a microtubule binding protein, as one of dozens of genes necessary for CD61 expression. Clip2 inhibition decreased surface CD61 expression, reduced expression of osteocyte-specific genes Dmp1 and Sost, and impaired dendrite morphology in vitro. Together, these results highlight the utility of surface CD61 as a marker of osteocyte maturity and identify a role of the microtubule cytoskeleton for osteocyte differentiation, form, and function. high

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Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

PubMed

A genome-wide CRISPR screen finds Clip2 as a new controller of bone cell development and shape

Abstract

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Abstract

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