The role of statins in the differentiation and function of bone cells

Abstract

Background Statins are 3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low‐density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL‐cholesterol (LDL‐C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL‐C‐lowering impact, statins also have other so‐called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation. Design The most relevant papers on the bone‐related ‘pleiotropic’ effects of statins were selected following literature search in databases and were reveiwed. Results Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein‐2 (BMP‐2), glucocorticoids, transforming growth factor‐beta (TGF‐β), alkaline phosphatase (ALP), type I collagen and collagenase‐1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation. Conclusion This review summarizes the literature exploring bone‐related ‘pleiotropic’ effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis.

Age-Influenced Receptors of Advanced Glycation End Product Overexpression Associated With Osteogenic Differentiation Impairment in Patients With Type 2 Diabetes

“…Therefore, it is reasonable to state that ACEI or ARB usage is not a contributory factor in the maintenance of osteogenic differentiation shown in DM-pD. Statins have been previously shown to have beneficial effects on bone metabolism and osteoporosis ( 55 – 58 ). Statins have been demonstrated to promote osteoblast differentiation and bone formation by stimulating the Akt/PI3 kinase and the β-catenin/Wnt signaling pathway, as well as to inhibit osteoblast apoptosis via activation of the TGFβ/Smad3 pathway ( 55 ).…”

“…Statins have been previously shown to have beneficial effects on bone metabolism and osteoporosis (55)(56)(57)(58). Statins have been demonstrated to promote osteoblast differentiation and bone formation by stimulating the Akt/PI3 kinase and the b-catenin/Wnt signaling pathway, as well as to inhibit osteoblast apoptosis via activation of the TGFb/Smad3 pathway (55). Zhang M and colleagues (56) demonstrated that simvastatin promoted differentiation of rat mesenchymal stem cells toward osteoblasts through the upregulation of b-catenin (56).…”

Abnormal Lipid Profile in Fast-Growing Broilers With Spontaneous Femoral Head Necrosis

“…As the plasma TC concentration increases, the bone density decreases. Clinically, statins are used to antagonize osteoporosis ( Chamani et al, 2021 ). In addition, the inflammatory microenvironment caused by fat has a stimulating effect on the formation of bone cells, releasing a large number of inflammatory factors, aggravating the destruction of cartilage damage and synovial inflammation, and increasing the incidence of arthritis ( Pousinis et al, 2020 ).…”

Biomolecules Orchestrating Cardiovascular Calcification

“…Paradoxically, certain treatments, such as statins and high-intensity exercise, which reduce cardiovascular events, have been shown to increase the progression of CAC [175][176][177]. The mechanisms by which statins affect bone and mineral formation have been reviewed by Chamani and colleagues [178]. These include the increased expression of factors that mediate bone metabolism, including bone morphogenetic protein-2, transforming growth factor-beta, TNAP, and type I collagen.…”