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

Maha Sabry,Seham Mostafa,Laila Rashed,Suzanne Estaphan,Samaa Kamar,Sridhar Muthusami

doi:10.1371/journal.pone.0258254

Abstract

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.

Highlights

Menopause has an average onset around 50s, with increasing longevity
These results may be denoting the potential role of these molecules in osteoporosis pathogenesis yet we found no significant changes in RANKL/OPG ratio among all groups
On reviewing the results of correlation to identify factors most strongly correlated with MMP9 expression, beside the significant correlations previously illustrated between matrix metalloproteinase-9 (MMP-9) gene expression and bone turnover markers and mediators, the present study revealed a significant correlation between Matrix metalloproteinase (MMP)-9 gene expression and dyslipidemia and inflammation markers, which represent major risk factors for cardiovascular disease (CVD)

Summary

Introduction

Menopause has an average onset around 50s, with increasing longevity. It could be considered a midlife event that presents an enormous healthcare problem due to its long-term complications. Osteoporosis (OP) affects 1 in 3 women, hip fracture has a high morbidity and mortality, and, cardiovascular disease (CVD) is the first cause of women death worldwide [1]. Osteoporotic patients have been found to be more prone to attain ischaemic heart diseases and likewise patients with CVS have been shown to be more prone for osteoporosis. Researchers suggested a causal relationship between both pathologies [2,3,4]. There is a tremendous need to identify the molecular link between both conditions in order to reach a treatment capable to efficiently address them simultaneously

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