共 1 条
Dual Effect of Platelet Lysate on Human Articular Cartilage: A Maintenance of Chondrogenic Potential and a Transient Proinflammatory Activity Followed by an Inflammation Resolution
被引:0
|作者:
Pereira, Rui Cruz
[1
,3
]
Scaranari, Monica
[4
]
Benelli, Roberto
[4
]
Strada, Paolo
[4
]
Reis, Rui L.
[2
,3
]
Cancedda, Ranieri
[1
,4
]
Gentili, Chiara
[1
,4
]
机构:
[1] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy
[2] Univ Minho, Res Grp Biomat Biodegradables & Biomimet 3Bs, Headquarters European Inst Excellence Tissue Engn, P-4719 Braga, Portugal
[3] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal
[4] AOU San Martino IST Ist Nazl Ric Canc, I-16132 Genoa, Italy
关键词:
GELATINASE-ASSOCIATED LIPOCALIN;
NF-KAPPA-B;
RICH PLASMA;
GROWTH-FACTOR;
CHONDROCYTES;
COX-2;
BONE;
EXPRESSION;
CYCLOOXYGENASE-2;
INHIBITION;
D O I:
10.1089/ten.tea.2012.0225
中图分类号:
Q813 [细胞工程];
学科分类号:
摘要:
Platelet-rich plasma (PRP), a cocktail of platelet growth factors and bioactive proteins, has been proposed as a therapeutic agent to restore damaged articular cartilage. We report the biological effect of the platelet lysate (PL), a PRP derivative, on primary human articular chondrocytes cultured under both physiological and inflammatory conditions. When added to the culture medium, PL induced a strong mitogenic response in the chondrocytes. The in vitro expanded cell population maintained a chondrogenic redifferentiation potential as revealed by micromass culture in vitro and ectopic cartilage formation in vivo. Further, in chondrocytes cultured in the presence of the proinflammatory cytokine interleukin-1 alpha (IL-1 alpha), the PL induced a drastic enhancement of the synthesis of the cytokines IL-6 and IL-8 and of neutrophil-gelatinase associated lipocalin, a lipocalin expressed during chondrocyte differentiation and inflammation. These events were mediated by the p38 MAP kinase and NF-kappa B pathways. We observed that inflammatory stimuli activated phospo-MAP kinase-activated protein kinase 2, a direct target of p38. The proinflammatory effect of the PL was a transient phenomenon; after an initial upregulation, we observed significant reduction of the NF-kappa B activity together with the repression of the inflammatory enzyme cyclooxygenase-2. Moreover, the medium of chondrocytes cultured in the simultaneous presence of PL and IL-1 alpha, showed a significant enhancement of the chemoattractant activity versus untreated chondrocytes. Our findings support the concept that the platelet products have a direct beneficial effect on articular chondrocytes and could drive in sequence a transient activation and the resolution of the inflammatory process, thus providing a rational for their use as therapeutic agents in cartilage inflammation and damage.
引用
收藏
页码:1476 / 1488
页数:13
相关论文