Role of matrix metalloproteinase-9 in the pathogenesis of osteoporosis in patients with chronic obstructive pulmonary disease


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Abstract

Aim. To determine a relationship between matrix metalloproteinase-9 (MMP-9) activity and its tissue inhibitors TIMP-1 and 2, tumor necrosis factor-α (TNF-α), bone mineral density (BMD), and bone exchange in chronic obstructive pulmonary disease (COPD). Subjects and methods. Seventy-six patients with COPD and 20 healthy volunteers were examined using dual-energy X-ray absorptiometry n the lumbar spine (LII-LIV) and femoral neck (FN). The serum levels of MMP-9, TIMP-1 and TIMP-2, TNF-α, and Β-Crosslaps (ΒCL) were measured. Results. There was a higher MMP-9 level in COPD than that in the controls ((383.8±54.2 and 137.6±31.4 pg/ml, respectively; p<0.01). The levels of TIMP-1 and TIMP-2 were not different from those in the control group. An inverse correlation was found between forced expiratory volume in one second (FEV1) and MMP-9 concentration (r= -0.59; p=0.002) and a positive correlation with smoking index (r=0.47; p=0.04). There was an inverse correlation between MMP-9 concentration and BMD in both LII-LIV and FN (r= -0.67; p<0.001 and r= -0.61; p<0.01, respectively) and a direct correlation with ΒCL (r=0.53; p=0.04). An inverse correlation was established between TNF-α and T index in both LII-LIV (r =-0.54; p<0.01) and FN (r= -0.48; p<0.01). At the same time, the level of TNF-α directly correlated with the bone resorption marker ΒCL (r=0.53; p=0.002) and MMP-9 (r=0.57; p=0.003). Conclusion. Elevated MMP-9 levels may play an important role in type I collagen degradation, giving rise to enhanced bone resorption in COPD.

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Роль матриксной металлопротеиназы-9 в патогенезе остеопороза у пациентов с хронической обструктивной болезнью легких. - Резюме. Цель исследования. Определить взаимосвязь между активностью матричной металлопротеазы (ММР-9) и тканевыми ингибиторами (TIMP)-1 и 2, α-фактором некроза опухоли (α-ФНО), минеральной плотностью костной ткани (МПКТ) и обменом костной ткани при хронической обструктивной болезни легких (ХОБЛ). Материалы и методы. Обследовали 76 пациентов с ХОБЛ и 20 здоровых добровольцев. МПКТ исследовали с помощью двухэнергетической рентгеновской абсорциометрии (DEXA) в поясничном отделе позвоночника (LII-LIV) и шейке бедренной кости (ШБК). В сыворотке крови определяли уровни ММР-9, (TIMP)-1 и 2, ü-ФНО, ΒCrosslaps (ΒCL). Результаты. Отмечено повышение уровня ММP-9 при ХОБЛ по сравнению с контролем (383,8±54,2 и 137,6±31,4 пг/мл соответственно; p<0,01). Уровни TIMP-1 и 2 достоверно не отличались от аналогичных показателей контрольной группы. Обнаружена обратная корреляция между ОФВ1 и концентрацией MMP-9 (r= -0,59; p=0,002) и положительная корреляция с индексом курящего человека (r= -0,47; p=0,04). Выявлена обратная корреляция между концентрацией MMP-9 и МПКТ как в LII-LIV, так и в ШБК (r= -0,67; p<0,001 и r= -0,61; p<0,01 соответственно) и прямая связь с ΒCL (r=0,53; p=0,04). Установлена обратная корреляция между α-ФНО и Т-критерием как LII-LIV (r= -0,54; p<0,01), так и в ШБК (r= -0,48; p<0,01). При этом уровень α-ФНО прямо коррелировал с маркером резорбции костной ткани ΒCL (r=0,53; p=0,002) и с MMP-9 (r=0,57; p=0,003). Заключение. Повышение уровня MMP-9 может играть важную роль в деградации коллагена 1-го типа, что приводит к усилению резорбции кости при ХОБЛ.
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