DOI: 10.4103/ijem.ijem_691_25 ISSN: 2230-8210

Rap1A Inhibition Alters Osteogenic and Angiogenic Gene Expression in MG-63 Osteoblast-like Cells

Remya James, Vineeth T.V. Kumar, Febby Payva, K. S. Santhy
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Abstract

Introduction:

The role of RAP1A , widely implicated in osteoblast differentiation, is not fully understood. Therefore, the present study investigated how the inhibition of Rap1A -associated prenylation pathways affects gene expression profiles associated with osteogenesis and angiogenesis.

Methods:

The MG-63 cell line was treated with a selective RAP1A protein inhibitor (GGTI298–3 µM, 24 h), and osteogenic and angiogenic gene expression was assessed.

Results:

Pharmacological perturbation (GGTI298 treatment) of Rap1A-associated prenylation pathways led to broad suppression of key osteogenic differentiation markers, including bone morphogenetic protein 2, alkaline phosphatase, collagen type I alpha 1 chain and the transcription factor osterix. GGTI298 treatment also resulted in a dramatic reduction in RAP1A mRNA (~290-fold). FOXO1 , AMPK and VEGFA were downregulated. Notably, the master osteogenic regulator RUNX2 was upregulated (~12-fold).

Conclusion:

The downregulation of FOXO1 and AMPK suggests altered expression of genes associated with cellular energy sensing. VEGFA expression was reduced after GGTI298 treatment, possibly indicating disruption of angiogenic signalling. Downregulation of osteogenic differentiation markers indicates a potential association between Rap1A -associated pathways and osteogenic gene regulation, suggesting their involvement in molecular mechanisms relevant to bone biology.

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