O Krasnova, P Semenova, A Kovaleva, J Sopova, V Turilova, T Yakovleva, O Bystrova, M Martynova, I Neganova
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引用次数: 0
Abstract
Osteoporosis is a complex multifactorial bone disease with a strong genetic component. Among the various genes implicated in the progression of osteoporosis, those encoding G-protein-coupled receptors (GPCRs) play a crucial role in its pathogenesis. This superfamily of membrane receptors regulates myriad of cellular events including physiological and pathological processes in bone tissue. Beta-2-adrenergic receptor (a member of the GPCR superfamily) mediates cues from sympathetic nervous system to the bone tissue being expressed on both types of bone cells osteoblasts and osteoclasts. While the impact of this receptor typically investigated using animal models, the human gene ADRB2 coding beta-2-adrenergic receptor harbors numerous non-synonymous single-nucleotide polymorphisms (SNPs) that alter the activity of the receptor. One of the most prevalent SNP is c.46G > A; however, its impact on bone homeostasis has only been explored in epidemiological studies with results showing considerable variability. In this study, we generated for the first time induced pluripotent stem cells (iPSCs) line from the patient with osteoporosis carrying c.46G > A in ADRB2. This new cell line exhibits hallmarks of pluripotency, normal karyotype, and ability to differentiate into three-germ layers. Furthermore, we conducted a comparative analysis of ADRB2 expression between newly obtained iPSCs and those derived from healthy donors. This comparison extended to mesenchymal stem cells (iMSCs) derived from these iPSC lines, assessing both basal and osteogenic conditions at the mRNA and protein levels. Our findings revealed that iMSCs from an osteoporotic patient with the c.46G > A in ADRB2 exhibited decreased ADRB2 expression, which correlated with a diminished potential for osteogenic differentiation. Newly obtained iPSCs line represents a promising cell source for in vitro osteoporosis model and offers the possibility to study in-depth the specific impact of c.46G > A in ADRB2 on osteoporosis pathogenesis.
期刊介绍：
Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well.
Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format.
Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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