Correlation of Circulating Matrix Metalloproteinase-3 and Osteopontin Levels with Postmenopausal Osteoporosis

Abstract

Osteoporosis is a metabolic condition characterized by decreased bone mass and strength due to increased bone turnover, which compromises bone architecture and results in increased fracture risk. Postmenopausal osteoporosis is the most common type of osteoporosis associated with estrogen deficiency [1]. However, the mechanisms by which estrogen deficiency causes bone loss are complex and are not fully understood. Matrix metalloproteinase (Matrix Metalloproteinase, MMP) forms a family of zinc-dependent proteinases essential for several physiological and pathological events, such as embryonic development, angiogenesis, wound repair, periodontal disease, rheumatoid arthritis, cancer invasion, and metastasis. Osteoblast-derived MMPs have been shown to play a role in bone metabolism by degradation of the bone matrix. Bone resorption is dependent on the activity MMP-3, which degrades denatured type Ⅱ collagen and other components of the bone organic matrix. Evidence has accumulated for an active participation by osteoblast-derived MMPs in the initiation of bone resorption and coupled bone formation by degrading the unmineralized osteoid layer of the bone surface to allow osteoclasts to attach to the mineralized matrix. In vitro [2,3], normal osteoblasts secrete abundant MMP-3 which was triggered by osteopontin (OPN), then OPN-MMP-3 complex were existed to induce bone matrix into ossification before bone mineralization. Methods Subjects The study population comprised 120 postmenopausal women aged 48-65 years, selected randomly from Wuhan, China and its surrounding area. All subjects were screened by means of a detailed questionnaire, medical history taking, and physical examination. Menopause was defined as 1 year with no menstrual flow. Subjects were excluded from the study if they had oligomenorrhea or a menorrhea before the age of 40 years or if they had such conditions affecting bone metabolism as diseases of the kidney, liver, parathyroid, or thyroid, diabetes mellitus, hyperprolactinemia, oophorectomy, rheumatoid arthritis, ankylosing spondylitis, malabsorption syndromes, malignant tumors, hematologic diseases, previous pathological fractures, hypertension, coronary artery disease, angiopathy, myocardial infarction, cerebral infarction, and infectious disease. If the subjects had received treatment with glucocorticoids, estrogens, thyroid hormone, parathyroid hormone, fluoride, bisphosphonate, calcitonin, thiazide diuretics, barbiturates, anti-seizure medication, vitamin D and calcium-containing drugs, they were also excluded. Body height and weight were measured using a stadiometer and a standardized balance-beam scale, respectively. This study was approved by the Research Ethics Committee of Wuhan Union Hospital, and informed consent was obtained from each woman before the study. Among the postmenopausal women, 40 were considered osteoporosis according to the WHO criterion: Bone Mineral Density (BMD) more than 2.5 SD below the normal adult mean based on the established reference databases. 40 women whose BMD was less than 1.0 SD below the normal were included into the normal group.40 volunteers were osteopnia whose BMD were between 2.5 SD and 1.0 SD. Abstract Objective: To study Matrix Metalloproteinase-3 (MMP-3) and Osteopontin (OPN) levels and correlations of MMP-3 and OPN with Bone Metabolic Markers and Bone Mineral Density (BMD) in postmenopausal Chinese women. Methods: MMP-3, OPN Osteoprotegrin (OPG), Osteoprotegrin Ligand (OPGL) of 120 postmenopausal Chinese female volunteers was measured using ELISA. BMD were measured using dual energy X-ray absorptiometry. According to the criteria of WHO, women were divided into 3 groups, such as normal, oteopenia and osteoporosis group. Results: OPN concentrations were significantly higher in osteoporosis (56 ± 20) ng/ml than normal (26 ± 11) ng/ml (P<0.05). But MMP-3 concentrations were little higher in osteoporosis (153 ± 121) ng/ml than normal (125 ± 101) ng/ml. In osteoporosis, notable negative correlations between OPN, ratio of OPN/MMP-3 and BMD, sOPGL were found (P<0.05) as well as positive relations between OPN, ratio of OPN/MMP-3 and sOPG (P<0.05), and positive relation of MMP-3 and BMD of Ward's triangle was existed (P<0.05), in osteopenia negative relations of MMP-3 and BMD as well as ratio of OPN/MMP-3 were detected (P<0.05).Conclusion: There are significant correlations between serum OPN, ratios of OPN and MMP-3 and bone biomarkers of sOPG, sOPGL, OPN and OPN/MMP-3 may increase with high bone-metabolism. The increases of OPN and ratio of OPN/MMP-3 appear possibly as a concomitant event in high bone turnover state, such as postmenopausal osteoporosis.