Ghrelin prevents articular cartilage matrix destruction in human chondrocytes

Liu, Jie; Cao, Lie; Gao, Xueming; Chen, Zhuo; Guo, Shifang; He, Zongru; Qian, Yaowen; Yu, Yongzhi; Wang, Gang

doi:10.1016/j.biopha.2017.12.050

Cited by 36 publications

(37 citation statements)

References 29 publications

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“…TNF‐α is identified to contribute to chondrocyte apoptosis, thus stimulating chondrocytes to release cartilage‐degrading enzymes, such as metalloproteinases . Previous studies have shown that ghrelin exercises its potent anti‐inflammatory effect through inhibition of pro‐inflammatory cytokines such as MMP‐3 and TNF‐α . These findings of anti‐inflammatory and cartilage‐protective properties suggest that ghrelin might have a potential therapeutic effect in the treatment of OA.…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, ghrelin has been proven to prevent OA. In an in vitro study conducted by Liu et al, ghrelin could inhibit interleukin‐1β mediated expression of A disintegrin and metalloproteinase with thrombospondin motifs 4, matrix metalloproteinase‐3 (MMP‐3), metalloproteinase‐3, and A disintegrin and metalloproteinase with thrombospondin motifs 5 and the degradation of aggrecan and type II collagen in human chondrocytes . In addition, systemic and local delivery of ghrelin markedly ameliorated the OA severity in both surgically induced OA models, which implied a protective function of ghrelin in the degeneration of articular cartilage .…”

Section: Introductionmentioning

confidence: 93%

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Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Zou

Yang³

et al. 2019

BioFactors

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Post‐traumatic osteoarthritis (PTOA) of ankle joints results in pain and reduced joint function. Ghrelin, a 28‐amino‐acid polypeptide, has been previously identified as the first cognate natural ligand that binds to the growth hormone secretagogue receptor. In the present study, ghrelin has been validated to exert cartilage‐protective and anti‐inflammatory effects. The current study was aimed at investigating the potential role of the levels of serum and synovial fluid (SF) ghrelin on the severity of disease in patients suffering from ankle PTOA. Ninety‐seven patients with ankle osteoarthritis who received an arthroscopical examination and debridement or replacement of the ankle joint were included in the study cohort. Meanwhile, 95 healthy individuals (whose age and sex were matched) who received periodic body checkups were enrolled as healthy controls. Enzyme‐linked immunosorbent assay (ELISA) was used to analyze the ghrelin levels in serum and SF. SF was also probed for cartilage degradation enzyme matrix metalloproteinases‐3 (MMP‐3) and tumor necrosis factor alpha (TNF‐α), which is a known pro‐inflammatory cytokine. The clinical evaluation was carried out using the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot rating scale and visual analogue scale (VAS). The radiographic severity was evaluated using the modified Kellgren–Lawrence (K–L) grading system. We scored for the modified Mankin's score to depict histopathological changes due to cartilage lesions. The diagnostic relevance of the ghrelin concentrations in the prediction of the radiographic grading (in comparison with MMP‐3 and TNF‐α) was evaluated by calculating the area under the curve of the receiver operating characteristic (ROC) curve. The serum abundance of ghrelin was not significantly altered between ankle PTOA patients and healthy controls. SF ghrelin was negatively correlated with radiographic progression determined by modified ankle K–L grades. In addition SF ghrelin concentrations were negatively related to VAS scores, and positively associated with AOFAS ankle‐hindfoot rating. Moreover, SF ghrelin was inversely proportional to the expressions of MMP‐3 and TNF‐α. ROC analysis curve demonstrated that ghrelin serves as a favorable marker for the diagnosis of radiographic severity by modified ankle K‐L grade. The ghrelin concentration in SF is negatively proportional to disease progression in patients suffering from ankle PTOA. Local administration of ghrelin may function as a decent adjuvant therapy to delay the progress of ankle PTOA. © 2019 BioFactors, 45(3):463–470, 2019

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Zou

Yang³

et al. 2019

BioFactors

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“…Although a large number of different agents have been reported to promote chondrogenic differentiation, very few of these have the potential to be effective within in vivo studies . Furthermore, ghrelin at the dose used have been shown to reduce inflammatory cytokine induced expression of matrix proteinases and ameliorated degradation of type II collagen and aggrecan . Moreover, we observed an increase in collagen I deposition (which is a marker of fibrocartilage formation) in animals treated with high concentrations of TGF‐β (Fig.…”

Section: Discussionmentioning

confidence: 77%

Enhancement of the chondrogenic differentiation of mesenchymal stem cells and cartilage repair by ghrelin

Fan

Chen

Tao

et al. 2019

Journal Orthopaedic Research

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Transforming growth factor beta (TGF‐β) is commonly utilized in chondrogenic differentiation protocols, but this often results in incomplete maturation of the derived chondrocytes. Gene expression analysis, quantitation of sulfated glycosaminoglycan and collagen, and histological staining were performed to assess the effects of ghrelin. The signaling pathways involved were investigated with inhibitors or targeted by shRNAs. Joint cavity delivery of TGF‐β with or without ghrelin, within a rat cartilage defect model was performed to evaluate the in vivo effects of ghrelin. Ghrelin dramatically enhanced gene expression levels of SOX9, ACAN, and COL II and resulted in increased synthesis of sulfated glycosaminoglycan (sGAG) and collagen in vitro. Combined treatment with TGF‐β and ghrelin synergistically enhanced the phosphorylation of ERK1/2 and DMNT3A, which accounted for increased expression of chondrogenic genes. Delivery of ghrelin in combination with TGF‐β after MSC implantation within a rat osteochondral defect model significantly enhanced de novo cartilage regeneration, as compared to delivery with TGF‐β alone. In conclusion, ghrelin could significantly enhance MSC chondrogenic differentiation in vitro and can also enhance cartilage regeneration in vivo when used in combination with TGF‐β. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1387–1397, 2019.

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“…STAT proteins are involved in mediating cellular responses to cytokines [44]. Recently, Liu et al and Latourte et al demonstrated activation of the STAT3 pathway in human chondrocytes and destabilization of the medial meniscus in a mouse model of OA [45,46]. The phosphorylated STAT3 (phospho-STAT3)-positive chondrocytes increased six weeks after destabilization of the medial meniscus (DMM), and administration of Stattic, an inhibitor of STAT3, significantly inhibited IL-6-induced chondrocyte apoptosis and phosphorylation of STAT3 in chondrocytes when compared with controls [46].…”

Section: Discussionmentioning

confidence: 99%

A Novel Rat Model of Patellofemoral Osteoarthritis Due to Patella Baja, or Low-Lying Patella

et al. 2019

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Background Patella baja, or patella infera, consists of a low-lying patella that results in a limited range of motion, joint pain, and crepitations. Patellofemoral joint osteoarthritis (PFJOA) is a subtype OA of the knee. This study aimed to develop a reproducible and reliable rat model of PFJOA. Material/Methods Three-month-old female Sprague-Dawley rats (n=24) included a baseline group (n=8) that were euthanized at the beginning of the study. The sham group (n=8), and the patella ligament shortening (PLS) group (n=8) were euthanized and evaluated at ten weeks. The PLS model group (n=8) underwent insertion of a Kirschner wire under the patella tendon to induce patella baja. At ten weeks, the sham group and the PLS group were compared using X-ray imaging, macroscopic appearance, histology, immunohistochemistry, TUNEL staining for apoptosis, and micro-computed tomography (micro-CT). The patella height was determined using the modified Insall-Salvati (MIS) ratio. Results The establishment of the rat model of patella baja in the PLS group at ten weeks was confirmed by X-ray. In the PLS group, patella volume, sagittal length, and cross-sectional area were significantly increased compared with the sham group. The PFJ showed typical lesions of OA, confirmed macroscopically and histologically. Compared with the sham group, in the rat model of PFJOA, there was increased cell apoptosis, and immunohistochemistry showed increased expression of biomarkers of osteoarthritis, compared with the sham group. Conclusions A rat model of PFJOA was developed that was confirmed by changes in cartilage and subchondral bone.

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Ghrelin prevents articular cartilage matrix destruction in human chondrocytes

Cited by 36 publications

References 29 publications

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Enhancement of the chondrogenic differentiation of mesenchymal stem cells and cartilage repair by ghrelin

A Novel Rat Model of Patellofemoral Osteoarthritis Due to Patella Baja, or Low-Lying Patella

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