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Early supplemental ?2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model.

ABSTRACT: OBJECTIVE:To determine if early supplemental intra-articular ?2-macroglobulin (A2M) has a chondroprotective effect in a collagen II-induced arthritis (CIA) mice model. METHODS:DBA/1 mice were randomized into four groups (n = 15/group): (a) CIA + 1.2 ?g of A2M; (b) CIA + 0.8 ?g of A2M; (c) CIA + 0.4 ?g of A2M; (d) vehicle + phosphate-buffered saline (PBS). A2M was injected into right ankles and PBS was injected into the left ankles simultaneously as internal control at days 36, 43 and 50. The CIA inflammation clinical score and ankle thickness were recorded every other day starting on day 21 until sacrifice. Changes in inflammation were monitored by in vivo fluorescence molecular tomography (FMT). Inflammation, cartilage and bone damage were assessed with X-ray, histology and immunohistochemistry. Cartilage and inflammation-related gene expression was quantified by real-time polymerase chain reaction (PCR). RESULTS:All mice showed ankle inflammation on day 33. After day 43, lower clinical scores, ankle thickness and Sharp/van der Heijde method scores in A2M-treated ankles compared with PBS-treated ankles. FMT data indicated that the inflammation markers MMPSense and ProSense were significantly elevated in the PBS-treated ankles than A2M-treated ankles. Histology and X-ray analyses indicated that A2M administration resulted in lower levels of inflammatory infiltration and synovial hyperplasia, as well as more typical cartilage and bone organization with increased COL II and Aggrecan staining when compared with PBS-treated ankles. In addition, real-time PCR showed that,matrix metalloproteinase-3, -9, -13, COL X and Runx2 were significantly less expressed in A2M-treated groups than PBS-treated animals. CONCLUSION:Early supplemental intra-articular A2M exerts an anti-inflammatory effect and attenuates cartilage and bone damage in a CIA model.

SUBMITTER: Li S

PROVIDER: S-EPMC6465088 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Early supplemental α2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model.

Li Shengchun S Xiang Chuan C Wei Xiaochun X Sun Xiaojuan X Li Ruifang R Li Pengcui P Sun Jian J Wei Dinglu D Chen Yong Y Zhang Yanxiang Y Wei Lei L

International journal of rheumatic diseases 20190104 4

<h4>Objective</h4>To determine if early supplemental intra-articular α2-macroglobulin (A2M) has a chondroprotective effect in a collagen II-induced arthritis (CIA) mice model.<h4>Methods</h4>DBA/1 mice were randomized into four groups (n = 15/group): (a) CIA + 1.2 μg of A2M; (b) CIA + 0.8 μg of A2M; (c) CIA + 0.4 μg of A2M; (d) vehicle + phosphate-buffered saline (PBS). A2M was injected into right ankles and PBS was injected into the left ankles simultaneously as internal control at days 36, 43 ...[more]

PMID: 30609267

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Project description:Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2‑macroglobulin (α2M) could prevent early‑stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate‑resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit‑8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase‑1 (HO‑1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8‑hydroxy‑2'‑deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase‑1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early‑stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

Dataset Information

Early supplemental ?2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model.

Publications

Early supplemental α2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model.

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