PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Bone & Joint Research Pub Date : 2024-04-01 DOI:10.1302/2046-3758.134.BJR-2023-0179.R2
Yung-Chang Lu, Tsung-Chuan Ho, Chang-Hung Huang, Shu-I Yeh, Show-Li Chen, Yeou-Ping Tsao
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Abstract

Aims: Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods: Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.

Results: The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC.

Conclusion: The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

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PEDF肽加透明质酸通过STAT3介导的软骨生成刺激骨关节炎软骨再生
目的:众所周知,色素上皮衍生因子(PEDF)可通过激活组织特异性干细胞诱导多种类型的组织再生。在此,我们研究了PEDF 29-mer肽对大鼠骨关节炎(OA)受损关节软骨(AC)的治疗潜力:方法:从大鼠骨髓(BM)中分离间充质干/基质细胞(MSCs),并评估29-mer对BM-MSCs培养过程中软骨分化的影响。通过在大鼠右膝(设定为第0天)关节内注射一次碘乙酸钠(MIA)诱导膝关节OA。29-mer溶于5%透明质酸(HA),分别于MIA注射后第8天和第12天在大鼠右膝关节内注射。随后,国际骨关节炎研究学会(OARSI)组织病理学评分系统和后爪重量分布变化分别评估了29-mer/HA对OA的治疗效果。通过5-溴-2'-脱氧尿苷(BrdU)和软骨标志物的双重免疫染色检测受损AC中软骨细胞的再生情况:结果:29-mer能促进在不同培养基中培养的BM-间充质干细胞的扩增和软骨分化。注射 MIA 会导致整个 AC 软骨细胞死亡,随后软骨变性。29-mer/HA 处理可诱导受损 AC 中广泛的软骨细胞再生,并抑制 MIA 诱导的滑膜炎,同时还能恢复软骨基质。PEDF受体(PEDFR)和信号转导和激活转录3(STAT3)信号的药理抑制剂大大阻断了29-mer对培养的BM-间充质干细胞和损伤的AC的软骨促进活性:结论:29-mer/HA 配方能有效诱导受损 AC 的软骨细胞再生和软骨基质的形成。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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