Anti-osteoporotic effects of tetramethylpyrazine via promoting osteogenic differentiation and inhibiting osteoclast formation

Abstract

Long‑term glucocorticoid therapy results in various side effects, including a high incidence of glucocorticoid‑induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis. Excess glucocorticoids reduce the viability of bone marrow‑derived mesenchymal stem cells (BMSCs) and prolong osteoclast survival. These two types of cell are essential in the balance between bone formation and resorption. Tetramethylpyrazine (TMP), the pharmacologically active component extracted from Chuanxiong, has been reported to protect BMSCs from glucocorticoid‑induced apoptosis. In the present study, the protective effects of TMP on BMSC differentiation and osteoclasts maturation in GIOP were investigated in vivo and in vitro. The immunostaining of osterix (OSX) and tartrate‑resistant acid phosphatase (TRAP) staining indicated that TMP promoted osteogenesis and inhibited osteoclastogenesis in a rat model of GIOP. Treatment with 10‑6 M dexamethasone (Dex) significantly inhibited BMSC differentiation and increased TRAP‑positive cells in vitro. However, different concentrations of TMP (50, 100 and 200 µM) ameliorated the negative effects of Dex by promoting the activity of alkaline phosphatase (ALP) and the calcium mineralization of BMSCs following osteogenic induction, which increased the expression levels of osteogenic genes, including ALP, collagen type I α1, osteocalcin and OSX, and decreased osteoclastogenesis‑related genes, including TRAP, nuclear factor of T‑cells cytoplasmic 1 and cathepsin K. In addition, it was found that the inhibition of receptor activator of nuclear factor‑κB ligand and intereleukin‑6 in BMSCs may be a possible mechanism for the protective effects of TMP against glucocorticoid‑induced osteoclastogenesis. These results are the first, to the best of our knowledge, to demonstrate that TMP promotes BMSC differentiation and inhibits osteoclastogenesis to ameliorate bone mass change in GIOP.

Ligustrazine Exerts Cardioprotection in Animal Models of Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

“…Simultaneously, Lig can inhibit the expression of the endothelial cell adhesion molecule of E-selectin, P-selectin and intercellular adhesion molecule-1 (Yang et al, 2008 ). Ultimately, they can alleviate inflammatory of myocardial I/R injury through inhibiting the expression of tumor necrosis factor-α (Hu et al, 2008 ), IL- 6 (Hu et al, 2008 ; Shang et al, 2008 ; Wang et al, 2017 ), and/or promoting the expression of HSP (Chen et al, 2007 ; Shang et al, 2008 ); (3) inhibition of apoptosis (Duan et al, 2000 ; Chen et al, 2007 ; Zhang et al, 2007 ) through increasing the expression of Bcl-2 (Liu and Niu, 2011 ; Zhai et al, 2011 ; Zhao et al, 2012 ), reducing the expression of Bax protein (Liu and Niu, 2011 ; Zhai et al, 2011 ; Zhao et al, 2012 ) in the myocardium, and down-regulating the expression of caspase and Fas (Zhang et al, 2007 ); (4) metabolism mechanism through increasing the expression of the protein of p-Akt (Lv et al, 2012 , 2016 ) and content of ATP in myocardium (Lv et al, 2016 ) with activating PI3K/Akt signal pathway (Lv et al, 2012 , 2016 ); (5) improvement of the circulation by enhancing the expression of NO (Wan et al, 1998 ; Yang and Rui, 2007 ; Gu et al, 2009 ; Li and Li, 2010 ) via up-regulating the expression of NOS (Li et al, 2006 ; Xu and Zhang, 2006 ; Yang and Rui, 2007 ; Gu et al, 2009 ). A schematic representation of cardioprotective mechanism of Lig for myocardial I/R injury was summarized in Figure 10 .…”

Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition

“…The activity and number of osteoclasts after hydrogel injection were further examined by TRAP staining. TRAP, a metabolic enzyme specifically expressed by mature osteoclasts, is closely associated with osteolysis in osteoblasts . TRAP is expressed in osteoclasts, and the dark-stained cells with burgundy cytoplasm are osteoclasts.…”

“…TRAP, a metabolic enzyme specifically expressed by mature osteoclasts, is closely associated with osteolysis in osteoblasts. 38 TRAP is expressed in osteoclasts, and the dark-stained cells with burgundy cytoplasm are osteoclasts. Osteoclasts are effector cells of bone resorption.…”

The combination of two natural medicines, Chuanxiong and Asarum: A review of the chemical constituents and pharmacological activities

“…Further studies suggested that TMP down-regulated RANKL and IL-6, promoted osteogenesis and inhibited osteoclastogenesis to ameliorate the change in bone mass in the GIOP state. 54 In addition, LIG protected chondrocytes against SNP-induced apoptosis and delayed articular cartilage degeneration via suppression of the JNK and p38 MAPK pathways. 55 Recently, Dong et al 56 discovered that the CX ethanol extract (CXE) could be used to treat OP by attenuating cellular reactive oxygen species levels and inhibiting osteoblast apoptosis through PI3K/Akt signaling pathway.…”