Unraveling the Mechanism of Impaired Osteogenic Differentiation in Osteoporosis: Insights from <i>ADRB2</i> Gene Polymorphism
Olga Krasnova,
Julia Sopova,
Anastasiia Kovaleva,
Polina Semenova,
Anna Zhuk,
Daria Smirnova,
Daria Perepletchikova,
Olga Bystrova,
Marina Martynova,
Vitaly Karelkin,
Olga Lesnyak,
Irina Neganova
Affiliations
Olga Krasnova
Laboratory of Molecular Science, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Julia Sopova
Laboratory of Molecular Science, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Anastasiia Kovaleva
Laboratory of Molecular Science, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Polina Semenova
Laboratory of Molecular Science, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Anna Zhuk
Institute of Applied Computer Science, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO University), Saint Petersburg 197101, Russia
Daria Smirnova
Laboratory of Regenerative Biomedicine, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Daria Perepletchikova
Laboratory of Regenerative Biomedicine, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Olga Bystrova
Laboratory of Cell Morphology, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Marina Martynova
Laboratory of Cell Morphology, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Vitaly Karelkin
Russian Scientific Research Institute of Traumatology and Orthopedics Named After Roman Romanovich Vreden, Saint Petersburg 195427, Russia
Olga Lesnyak
Department of Family Medicine, North-Western State Medical University Named After Ilya Ilyich Mechnikov, Saint Petersburg 191015, Russia
Irina Neganova
Laboratory of Molecular Science, Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia
Osteoporosis is characterized by increased resorption and decreased bone formation; it is predominantly influenced by genetic factors. G-protein coupled receptors (GPCRs) play a vital role in bone homeostasis, and mutations in these genes are associated with osteoporosis. This study aimed to investigate the impact of single nucleotide polymorphism (SNP) rs1042713 in the ADRB2 gene, encoding the beta-2-adrenergic receptor, on osteoblastogenesis. Herein, using quantitative polymerase chain reaction, western immunoblotting, immunofluorescence assays, and flow cytometry, we examined the expression of ADRB2 and markers of bone matrix synthesis in mesenchymal stem cells (MSCs) derived from osteoporosis patient (OP-MSCs) carrying ADRB2 SNP in comparison with MSCs from healthy donor (HD-MSCs). The results showed significantly reduced ADRB2 expression in OP-MSCs at both the mRNA and protein levels, alongside decreased type 1 collagen expression, a key bone matrix component. Notably, OP-MSCs exhibited increased ERK kinase expression during differentiation, indicating sustained cell cycle progression, unlike that going to HD-MSC. These results provide novel insights into the association of ADRB2 gene polymorphisms with osteogenic differentiation. The preserved proliferative activity of OP-MSCs with rs1042713 in ADRB2 contributes to their inability to undergo effective osteogenic differentiation. This research suggests that targeting genetic factors may offer new therapeutic strategies to mitigate osteoporosis progression.
