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AMP‐activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low‐nutrition, low‐energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK‐activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.
AMP‐activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low‐nutrition, low‐energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK‐activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.
This study aimed to evaluate the correlation between BMAT and bone quality, describe the long-term effects of ovariectomy on bone, and investigate BMAT's spatial distribution. Fifteen-months-old female Sprague‒Dawley rats were studied, comparing ovariectomized (OVX, n = 22) and sham-operated (SHAM, n = 11) groups at 6 months. Tibias were analyzed for bone microarchitecture, BMAT (microcomputed tomography), mineral parameters (quantitative backscattered electron imaging), and bone composition (Raman microspectroscopy). The OVX tibias showed severe trabecular bone loss (lower bone volume/total volume, p < 0.001) with increased BMAT (higher adipose volume per marrow volume, p < 0.001), decreased mineral content (lower calcium concentration, p < 0.001), and altered organic components (lower mineral/matrix ratio in new bone, p = 0.03 trabecular surface, p < 0.001 trabecular core). When the data are pooled over both groups (SHAM and OVX), the adipose volume/marrow volume ratio was negatively correlated with bone volume/total volume (r = − 0.79, p < 0.001) and mineral/matrix ratio (r = − 0.37, p = 0.04 trabecular surface; r = − 0.65, p < 0.001 trabecular core) and positively correlated with crystallinity (r = 0.55, p = 0.001 trabecular surface; r = 0.49, p = 0.006 trabecular core). The mineral/matrix ratio of trabecular surface new bone was strongly negatively correlated with the adipose compartment nearest to the bone surface. These findings suggest mechanisms underlying BMAT's role in bone resorption.
INTRODUCTION: Diabetic osteoporosis (DOP) has gradually gained public attention. The clinical manifestations of DOP include bone mass loss, bone microstructural damage, and increased bone fragility. background: Diabetic osteoporosis (DOP) has gradually gained public attention. The clinical manifestations of DOP include bone mass loss, bone microstructural damage and increased bone fragility. Intracellular reactive oxygen species (ROS) production was significantly increased under high glucose (HG) conditions, with deleterious effects on bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Vitamin K2 (VK2) has been demonstrated to promote bone formation both in vitro and in vivo. However, its potential role in diabetes-induced osteoporosis remains unelucidated. METHOD: Intracellular reactive oxygen species (ROS) production was significantly increased under high glucose (HG) conditions, with deleterious effects on bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Vitamin K2 (VK2) has been demonstrated to promote bone formation both in vitro and in vivo. RESULT: However, its potential role in diabetes-induced osteoporosis remains unelucidated. This study aims to verify whether VK2 treatment could relieve the deleterious effects of high glucose on BMSCs and delay the progression of osteoporosis. The results revealed that the HG environment downregulated the expression of osteogenesis-related proteins. method: The protective effect of VK2 on BMSCs were evaluated by CCK-8, the mitochondrial function was detected by mitosox and JC-1. Osteogenic diferentiation potential was examined by alkaline phosphatase (ALP) staining and alizarin red s (ARS) staining.Simultaneously, we used an established diabetes-induced osteoporosis rat madel to assess the effects of VK2 in vivo. CONCLUSION: Correspondingly, VK2 treatment reversed the osteogenic phenotype of BMSCs under HG conditions. In addition, using an established diabetes-induced osteoporosis rat model, we found that VK2 administration could restore bone mass and microstructure. In conclusion, our results provide a promising therapeutic option in the clinical treatment of DOP. other: NO
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