TY - JOUR

T1 - Unraveling the Mechanism of Impaired Osteogenic Differentiation in Osteoporosis

T2 - Insights from ADRB2 Gene Polymorphism

AU - Krasnova, Olga

AU - Sopova, null

AU - Kovaleva, Anastasiia

AU - Semenova, Polina

AU - Zhuk, Anna

AU - Smirnova, Daria

AU - Perepletchikova, Daria

AU - Bystrova, Olga

AU - Martynova, Marina

AU - Karelkin, Vitaly

AU - Lesnyak, Olga

AU - Neganova, Irina

PY - 2024/12/20

Y1 - 2024/12/20

N2 - 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.

AB - 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.

KW - Humans

KW - Receptors, Adrenergic, beta-2/genetics

KW - Osteoporosis/genetics

KW - Osteogenesis/genetics

KW - Cell Differentiation/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Mesenchymal Stem Cells/metabolism

KW - Female

KW - Cell Proliferation/genetics

KW - Middle Aged

KW - Male

U2 - 10.3390/cells13242110

DO - 10.3390/cells13242110

M3 - Article

C2 - 39768200

VL - 13

JO - Cells

JF - Cells

SN - 2073-4409

IS - 24

M1 - 2110

ER -