ABSTRACT
BACKGROUND: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. METHODS: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1beta (IL-1beta) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. RESULTS: IL-1beta significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D. CONCLUSION: Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1beta stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1beta inhibition on TIMP-1 and TIMP-2 production.
Subject(s)
Humans , Collagen , Emphysema , Enzyme-Linked Immunosorbent Assay , Fibroblasts , Gelatin , Gels , Interleukin-1beta , Lung Diseases , Lung , Matrix Metalloproteinase 9 , Matrix Metalloproteinases , Polymerase Chain Reaction , Reverse Transcription , RNA, Messenger , Tissue Inhibitor of Metalloproteinase-1 , Tissue Inhibitor of Metalloproteinase-2 , Trypsin , Vitamin D , Wounds and InjuriesABSTRACT
Bisphosphonates (BPs) are a class of agent used to treat patient with osteoporosis or malignant bone metastases. BPs can be categorized into 2 groups: nitrogen-containing and non-nitrogen containing. Nitrogen-containing BPs are considered to have more toxicity. Despite their clinical benefits, bisphosphonate-related osteonecrosis of jaw(BRONJ) is a significant complication to patients receveing these drugs. Since the first description of BRONJ in 2003 by Marx, the number of reports on BRONJ has been rapidly increasing. BRONJ is considered as an emerging problem in oral & maxillofacial surgery. Generally, osteonecrosis in the maxilla is rare, however BRONJ is found both in the maxilla and the mandible. This is an important feature of BRONJ compared to common infectious osteomyelitis of the jaw. Growing number of case reports, suggest that bisphosphonate therapy may cause exposed, necrotic bone. BRONJ has simillar features compared to IORN (infected osteoradionecrosis). BRONJ has meaningful features established through the interestigation on histopathologic and radiographic findings. These features have an impact on treatment plan and prognosis. This presentation contemplates on features of histopathologic and radiographic findings in bisphosphonate-related osteonecrosis of the jaw.