Expression of matrix metalloproteinase-9 mRNA in osteoporotic bone tissues

Zhao, Haibo; Cai, Guoping; Du, Jun; Zhidao, Xia; Wang, Lan; Zhu, Tingyao

doi:10.1007/bf02887998

Cited by 25 publications

(10 citation statements)

References 8 publications

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“…A high expression of MMP-9 in osteoclasts has previously been detected (7). The present study demonstrated that, the levels of MMP-9 mRNA and protein expression in the OVX group were significantly higher in comparison with those in the sham group, which is consistent with the conclusions of a previous study (20). Similar trends were observed for MMP-9 expression as those detected for MMP-2 expression in the OVX group between 12 and 24 weeks after surgery.…”

Section: Discussionsupporting

confidence: 93%

Dynamic expression of matrix metalloproteinases�2, 9 and�13 in ovariectomy‑induced osteoporosis rats

et al. 2018

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The aim of the present study was to examine the dynamic expression of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 in an ovariectomy (OVX)-induced osteoporosis rat model. A total of 80 Sprague-Dawley female rats (age, 3 months) were randomly divided into the OVX and sham groups, with 40 rats in each group. Rats in the sham group received sham surgery, while the remaining rats were ovariectomized. After 12, 16, 20 and 24 weeks, 10 rats from each group were randomly sacrificed, respectively. It was observed that the bone mineral density (BMD) and the trabecular bone area in the OVX group were significantly lower as compared with those in the sham group (P<0.01). The expression levels of MMP-2 and MMP-9 were negatively correlated with the BMD, while MMP-13 was positively correlated with the BMD. The expression levels of MMP-2 and MMP-9 increased more abruptly and were significant higher in the OVX group in comparison with those in the sham group between 12 and 24 weeks after surgery (P<0.01). More specifically, the MMP-9 mRNA expression level in the OVX group increased abruptly between 12 and 24 weeks after surgery. By contrast, in the sham group, the MMP-9 mRNA level was undetectable between 12 and 16 weeks, and increased steadily between 16 and 24 weeks. Furthermore, the mRNA and protein expression levels of MMP-13 initially increased and then decreased in the OVX group (P<0.01 vs. the sham group), whereas they continuously increased in the sham group between 12 and 24 weeks after surgery. In conclusion, MMP-2, MMP-9 and MMP-13 regulated the development of osteoporosis, and MMP-9 may be used as an important marker in the early diagnosis of osteoporosis.

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Section: Discussionsupporting

confidence: 93%

Dynamic expression of matrix metalloproteinases�2, 9 and�13 in ovariectomy‑induced osteoporosis rats

et al. 2018

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“…In addition, no difference in the frequency of TNFα expression was observed in the bone tissue of OP versus healthy women [ 37 ]. Upregulation of MMP-9 gene and protein expression in the PBMCs of the examined OP women is supported by the in situ hybridization results of others, which showed an increase in MMP-9 mRNA in osteoporotic bone tissue versus the normal controls [ 3 ]. However, some studies also reported decreased MMP-9 expression in the bone of the postmenopausal OP patients [ 38 ].…”

Section: Discussionsupporting

confidence: 62%

“…Excessive bone degradation in OP is thought to result from an increased activity of resorptive osteoclasts, which express proteases such as metalloproteinase (MMP-9) and cathepsin K. Cathepsin K, a papain-like cysteine protease, is considered a key player in the process of bone resorption [ 3 , 4 ]. Osteoclast differentiation and function are regulated by the tumor necrosis factor α (TNF α ), receptor activator of nuclear factor kappa B ligand (RANKL), and macrophage colony-stimulating factor (M-CSF).…”

Section: Introductionmentioning

confidence: 99%

Association of Bone Loss with the Upregulation of Survival-Related Genes and Concomitant Downregulation of Mammalian Target of Rapamycin and Osteoblast Differentiation-Related Genes in the Peripheral Blood of Late Postmenopausal Osteoporotic Women

Tchetina

Maslova

Krylov

et al. 2015

Journal of Osteoporosis

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We aimed to identify bone related markers in the peripheral blood of osteoporotic (OP) patients that pointed toward molecular mechanisms underlying late postmenopausal bone loss. Whole blood from 22 late postmenopausal OP patients and 26 healthy subjects was examined. Bone mineral density (BMD) was measured by DXA. Protein levels of p70-S6K, p21, MMP-9, TGFβ1, and caspase-3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. OP registered by low BMD indices in late postmenopausal patients was associated with a significant upregulation of autophagy protein ULK1, cyclin-dependent kinase inhibitor p21, and metalloproteinase MMP-9 gene expression in the blood compared to the healthy controls and in a significant downregulation of mTOR (mammalian target of rapamycin), RUNX2, and ALPL gene expression, while expression of cathepsin K, caspase-3, transforming growth factor (TGF) β1, interleukin- (IL-) 1β, and tumor necrosis factor α (TNFα) was not significantly affected. We also observed a positive correlation between TGFβ1 and RUNX2 expression and BMD at femoral sites in these patients. Therefore, bone loss in late postmenopausal OP patients is associated with a significant upregulation of survival-related genes (ULK1 and p21) and MMP-9, as well as the downregulation of mTOR and osteoblast differentiation-related genes (RUNX2 and ALPL) in the peripheral blood compared to the healthy controls.

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“…Two major proteolytic enzyme classes, cathepsin k (a cysteine protease) and MMP 9 (a matrix metalloproteinase), are highly expressed during bone resorption leading to bone matrix degradation and are most abundant in osteoclasts (Logar et al 2007). Further, MMP 9 mRNA expression was reported to be higher in osteoporotic bone tissues compared with that of normal control group and is expressed by mono-and multinuclear osteoclasts and bone matrix lining cells (Haibo et al 1997). No significant difference was seen in MMP 14.…”

Section: Discussionmentioning

confidence: 92%

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone

Govindarajan

Khassawna

Kampschulte

et al. 2013

Int J Experimental Path

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Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.

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Expression of matrix metalloproteinase-9 mRNA in osteoporotic bone tissues

Cited by 25 publications

References 8 publications

Dynamic expression of matrix metalloproteinases�2, 9 and�13 in ovariectomy‑induced osteoporosis rats

Dynamic expression of matrix metalloproteinases�2, 9 and�13 in ovariectomy‑induced osteoporosis rats

Association of Bone Loss with the Upregulation of Survival-Related Genes and Concomitant Downregulation of Mammalian Target of Rapamycin and Osteoblast Differentiation-Related Genes in the Peripheral Blood of Late Postmenopausal Osteoporotic Women

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone

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