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    題名: 生長因子複合物促進透明質酸之骨關節炎治療潛能
    Therapeutic Potentials of Hyaluronic Acid Synergistically Enhanced by Platelet-rich Plasma for Osteoarthritis
    作者: 許維哲
    Hsu, Wei-Che
    貢獻者: 鄧文炳
    關鍵詞: 富含血小板血漿;玻尿酸;退化性關節炎
    Platelet-rich plasma;Hyaluronic acid;Osteoarthritis
    日期: 2013-06-17
    上傳時間: 2018-10-04 15:37:09 (UTC+8)
    摘要: 摘要
    骨關節炎是由於關節長期耗損、年齡老化或遺傳影響,造成軟骨組織生理失衡及關節組織瓦解所致。血小板富含血漿是由多種生長因子組成,在許多研究指出,具有促進軟骨細胞與軟骨組織再生之能力;同時,本實驗室先前研究也證實軟骨組織基質能顯著提高血小板富含血漿促進軟骨再生之能力。玻尿酸在軟骨組織基質中扮演潤滑緩衝的角色,在臨床應用之中,也已證實玻尿酸在骨關節炎治療中具有保水與抗發炎之功效,因此,我們相信血小板富含血漿合併玻尿酸具有加乘性或加成性地調控骨關節炎組織再生之能力。同時,結果指出在血小板富含血漿(PRP)中含有1ng/ml的TGF-beta1以及250ug/ml的玻尿酸(HA) 可以使軟骨細胞達到較高的細胞增生速率.我們利用前驅發炎因子IL-1beta+TNF-alpha造成軟骨特異性基因的抑制以及發炎基因的上升以建立發炎軟骨細胞模式,在訊息傳遞路徑中,HA/PRP之組成物可促進細胞膜上的接受器、細胞核中轉錄因子和特異性細胞外基質之蛋白表現,同時也可促進細胞外基質的沉澱,例如第二型膠原蛋白以及蛋白多糖.在人造立體關節炎組織培養,將軟骨細胞包埋在膠原蛋白支架培養在發炎的環境,會使細胞產生細胞死亡,而在HA/PRP處理下可有效回升其軟骨特異性基質的表現.最後,我們利用前十字韌帶去除建立骨關節炎小鼠模式,HA/PRP注射可有效加強軟骨細胞增生以及基質的沉降.從及時定量聚合脢連鎖反應分析中,HA/PRP的合併使用可有效降低發炎細胞激素和化學趨素在發炎軟骨細胞的表現.在未來,希望可作為血小板富含血漿合併玻尿酸可成為臨床關節炎治療之有效治療方法,並可成為極具治療潛力之新技術發展。
    Abstract
    Osteoarthritis (OA) is one of the crucial skeletal disorders characterized by the imbalanced homeostasis and destruction of the articular cartilage structure. Previous studies have demonstrated that platelet-rich plasma (PRP) composed of various growth factors would facilitate the recovery of chondrocytic degeneration and cartilage defect. We have previously demonstrated that extracellular matrix (ECM) could enhance the regenerative potentials of PRP in retrieving chondrogenic degeneration. In addition, hyaluronic acid (HA) plays a pivotal role in the water preservation and anti-inflammation in ECM of cartilage tissue. Hence, we hypothesize that the combination of HA and PRP would synergistically or additively manipulate the regeneration of OA tissue. First, the MTT result indicated that 1 ng/ml TGF-beta 1 in PRP and 250ug/ml HA showed optimal dosages for chondrocytes viability. The inhibition of chondrogenic-specific gene expression with IL-1beta+TNF-alpha was recovered by the HA/PRP treatment. The inflammatory molecules increase by IL-1beta+TNF-alpha were also highly down-regulated by HA with PRP. The membrane receptors TGFbetaIIR and CD44, signaling molecules phosphorylation such as Erk1/2 and Smad2/3, transcription factor Sox9 and specific ECM were strongly inhibited by IL-1beta+TNF-alpha and the strongly rescued by the combination of HA and PRP. In 3D osteoarthritis neo-cartilage model, the treatment of HA/PRP restored the type II collagen and proteoglycan from the inhibition of IL-1beta+TNF-alpha. In in vivo ACLT-induced OA animal model, intra-articular injections of HA/PRP can significantly also suppress the progression of OA in ACLT mice model. Overall, the combination of HA and PRP can enhance the regenerative and anti-inflammatory potentials and represents an advanced treatment for clinical OA therapy.
    描述: 碩士
    委員-李建和
    委員-林峯輝
    指導教授-鄧文炳
    資料類型: thesis
    顯示於類別:[生醫材料暨組織工程研究所] 博碩士論文

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