Background: Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Results: Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively. Conclusion: Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.

Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer’s and Parkinson’s, emphasizing the critical role of cerebral blood flow regulation and the blood–brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health.

Myostatin (MSTN), a member of TGF-β superfamily, is produced in the skeletal muscle to inhibit myocyte differentiation. MSTN expression is increased in the skeletal muscle in patients with chronic kidney disease (CKD), which may play a role in the pathogenesis of sarcopenia or in the protein energy wasting (PEW). This observation implies that the plasma MSTN level may be correlated with kidney function. Thus, we conducted a cross-sectional study to evaluate the association between the plasma MSTN concentration and the estimated glomerular filtration rate (eGFR). Subjects were 781 participants of a health examination performed in a rural area in Japan. Among them, 124 subjects were selected by stratified random sampling according to eGFR. Creatinine clearance (ClCr) by the Cockcroft-Gault equation was used as a measure of kidney function. Plasma concentration of MSTN was determined by ELISA. The plasma MSTN level was not different between men (3.42±1.61 ng/mL) and women (3.27±1.43 ng/mL). In a simple regression analysis, the MSTN level was significantly correlated with eGFR (r = -0.25, p<0.01) and ClCr (r = -0.20, p<0.05) but not with age and BMI. In a multiple linear regression analysis, the MSTN level showed a negative correlation with eGFR (standardized β = -0.31, p<0.01) and ClCr (standardized β = -0.35, p<0.01) under the adjustment with age, sex, BMI and LDL-C. Weak correlation was observed between the MSTN level and BMI / the serum LDL-C level. When the subjects were stratified into 4 groups according to eGFR, MSTN was significantly greater in the groups with the lowest and the 2^nd lowest eGFR (3.55±1.79 and 3.76±1.75 ng/mL, respectively) than the level in the group with the highest eGFR (2.77±0.85 ng/mL). Plasma MSTN level was elevated in an early stage of CKD, which could be involved in the progression of sarcopenia.