scholarly journals The cross-talk between matrix metalloproteinase-9, RANKL/OPG system and cardiovascular risk factors in ovariectomized rat model of postmenopausal osteoporosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258254
Author(s):  
Maha Sabry ◽  
Seham Mostafa ◽  
Samaa Kamar ◽  
Laila Rashed ◽  
Suzanne Estaphan

Epidemiology and pathogenesis of cardiovascular diseases (CVD) and osteoporosis are strikingly overlapping. This study presents matrix metalloproteinase-9 (MMP-9), as a simple molecular link more consistently associated with the pathophysiology of both osteoporosis and CVD risk factors. 40 adult female rats were randomly distributed into 4 groups [control sham-operated, untreated osteoporosis, carvedilol-treated osteoporosis and alendronate-treated osteoporosis]. After 8 weeks, blood samples were collected to estimate Lipid profile (Total cholesterol, HDL, Triglycerides), inflammatory markers (IL-6, TNF alpha, CRP and NO), and Bone turnover markers (BTM) (Alkaline phosphatase, osteocalcin and pyridinoline). The tibias were dissected to estimate MMP-9 and NF-kB gene expression, OPG, RANKL levels and for histological examination. Induction of osteoporosis resulted in a significant elevation in BTM, inflammatory markers and dyslipidemia. MMP-9 was significantly elevated and positively correlated with BTM, inflammation and dyslipidemia markers. Carvedilol and alendronate exerted a bone preservative role and attenuated dyslipidaemia and inflammation in accordance with their respective effect on MMP-9.

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0244650
Author(s):  
Maha Sabry ◽  
Seham Mostafa ◽  
Laila Rashed ◽  
Marwa Abdelgwad ◽  
Samaa Kamar ◽  
...  

Background Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats. Methods and findings 40 rats were randomly divided into 4 groups: control, untreated atherosclerosis group, atherosclerotic rats treated with carvedilol (10mg/kg/d) and atherosclerotic rats treated with alendronate sodium (10mg/kg/d). After 8 weeks, blood samples were collected for estimation of Lipid profile (Total cholesterol, HDL, TGs), inflammatory markers (IL-6, TNF-α, CRP and NO) and Bone turnover markers (BTMs) (Alkaline phosphatase, osteocalcin and pyridinoline). Rats were then euthanized and the aortas and tibias were dissected for histological examination and estimation of MMP-9, N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) and NF-kB expression. Induction of atherosclerosis via high fat diet and chronic stress induced a significant increase in BTMs, inflammatory markers and resulted in a state of dyslipidaemia. MMP-9 has also shown to be significantly increased in the untreated atherosclerosis rats and showed a significant correlation with all measured parameters. Interestingly, Carvedilol and bisphosphonate had almost equal effects restoring the measured parameters back to normal, partially or completely. Conclusion MMP-9 is a pivotal molecule that impact the atherogenic environment of the vessel wall. A strong cross talk exists between MMP-9, cytokine production and macrophage function. It also plays an important regulatory role in osteoclastogenesis. So, it may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats. Therefore, we suggest MMP-9 as a worthy molecule to be targeted pharmacologically in order to control both conditions simultaneously. Further studies are needed to support, to invest and to translate this hypothesis into clinical studies and guidelines.


2017 ◽  
Vol 54 (6) ◽  
pp. 584-593 ◽  
Author(s):  
Srilata Puru Naik ◽  
Mahesh P A ◽  
Jayaraj B S ◽  
SubbaRao V. Madhunapantula ◽  
Sarah Raeiszadeh Jahromi ◽  
...  

1997 ◽  
Vol 273 (3) ◽  
pp. C826-C833 ◽  
Author(s):  
G. Egidy ◽  
J. Friedman ◽  
M. Viswanathan ◽  
L. M. Wahl ◽  
J. M. Saavedra

CGP 42112, a high-affinity ligand for angiotensin II AT2 receptors, binds to rat macrophage/microglia lacking AT2 receptors. Here we report that CGP-42112 binds to human monocytes and exerts specific effects. Binding studies revealed a single site, highly specific for CGP-42112, not displaceable by angiotensin II, angiotensin fragments, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-10, transforming growth factor-beta, or lipopolysaccharide (LPS). Incubation of purified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen-coated dishes as well as matrix metalloproteinase-9 secretion. CGP-42112 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated secretion of TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 without affecting IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 activity. Additionally, CGP-42112 inhibited the increase in protein kinase A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor.


2006 ◽  
Vol 7 (3) ◽  
pp. 439-440
Author(s):  
R. Fagnani ◽  
M. Dell'Agli ◽  
S. Bellosta ◽  
G.V. Galli ◽  
R. Parente ◽  
...  

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