β-catenin is a key regulator of osteoblast differentiation, proliferation, and bone homeostasis. Through its interaction with transcription factors such as TCF/LEF, Runx2, and Osx, it coordinates gene expression essential for osteogenesis. The aim of this review is to demonstrate how β-catenin signaling is modulated by various physiological and pathological factors, including mechanical loading, oxidative stress, HIV-1 gp120, fluoride, implant topography, and microRNAs. These factors influence Wnt/β-catenin signaling through different mechanisms, often exerting opposing effects on osteoblast function. By integrating these modulators, we provide a comprehensive view of the dynamic regulation of β-catenin in bone biology. Understanding this complexity may provide insight into novel therapeutic strategies targeting β-catenin in bone regeneration, metabolic bone diseases, and pathologies such as HIV-associated bone loss or osteosarcoma.

Rhodiola rosea, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology.

The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia.

Rosavin, a glycoside isolated from Rhodiola rosea, exhibits various biological activities, including potential modulation of metabolic pathways. Despite promising findings in animal models, its effects on many human bone cells remain unexplored. This study aimed to investigate, for the first time, the in vitro effects of rosavin on human osteoblasts (HOBs), focusing on BMP-2 expression, cell morphology, and culture confluence as indicators of osteogenic activity. HOB cultures were treated with 50 µM or 100 µM rosavin for 21 days. BMP-2 expression was measured by ELISA, collagen production was assessed via Sirius Red staining, and cell morphology and confluence were evaluated using phase-contrast microscopy. A significant increase in BMP-2 expression was observed in the 100 µM rosavin group compared to the mineralization control (p < 0.05), particularly on days 14 and 21. Both rosavin-treated groups exhibited higher confluence than controls, with the 50 µM group showing unexpectedly greater confluence than the 100 µM group. Rosavin at 50 µM also promoted a cuboidal morphology characteristic of active HOBs. The presence of collagen validated both the successful progression of the mineralization process and the correct implementation of the experimental protocol. Rosavin enhances BMP-2 expression and supports HOB proliferation and morphological maturation in vitro. These findings suggest its potential as a supportive agent in the prevention or treatment of metabolic bone diseases. Further research is necessary to determine its bioavailability, safety profile, and therapeutic relevance in clinical settings.

Background: Rosavin, a bioactive compound derived from Rhodiola rosea , has been proposed to modulate osteoblast-associated signaling pathways. Emerging evidence highlights the role of CX3CL1 (fractalkine) in bone–immune interactions. This study aimed to investigate whether rosavin modulates CX3CL1 secretion and osteoblast morphology and confluence in human osteoblasts (HOB) in vitro, thereby providing descriptive cellular evidence relevant to CX3CL1-associated osteoblast responses under mineralizing conditions. Methods: Prior to biological testing, the chemical identity of rosavin was verified by high-resolution electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). HOB were cultured in growth medium (DMEM-g), mineralization medium (DMEM-m), or DMEM-m supplemented with rosavin at 50 µM (R50) or 100 µM (R100). Cell morphology and confluence were assessed by phase-contrast microscopy, supported by semi-quantitative image-based estimation of cell-covered area using Fiji/ImageJ. Sirius Red staining was performed only in the DMEM-m mineralization control group and was evaluated qualitatively as a supportive assessment of extracellular matrix maturation. Results: Rosavin was associated with dose- and time-dependent changes in CX3CL1 secretion and morphology-related observations in HOB cultures. The 50 µM rosavin condition showed significantly increased CX3CL1 secretion at days 14 and 21 compared with DMEM-m alone and was associated with higher cell confluence and predominance of cuboidal cell morphology. In contrast, the 100 µM condition was associated with lower apparent confluence, mixed cellular morphology, and reduced CX3CL1 secretion at later time points. Conclusions: These observations are descriptive, preliminary, and hypothesis-generating. Rosavin was associated with concentration-dependent modulation of CX3CL1 secretion and osteoblast morphological characteristics in vitro; however, the biological significance of CX3CL1 modulation in this monoculture model remains uncertain. Further mechanistic and functional studies are required.