Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler chondrocytes

Wang, Shoutang; Gao, Yingjie; Duan, Cuicui; Li, Dangdang; Tian, Xiaochen; QiaoLing, Zhang; Guo, Bin; Yue, Zhan‐Peng

doi:10.1002/cbin.10168

Cited by 9 publications

(8 citation statements)

References 28 publications

(40 reference statements)

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“…As the active form of MMP9, which can break down the denatured form of collagen type I, gelatin [13], was elevated on days of 2 and 3, showing that the matrix of the differentiating tissue turns into a cartilage specific matrix. MMP9 and MMP13 have been shown to be regulated by PTHrP and determine the matrix degradation of chondrocytes [34] and take part in normal cartilage morphology. MMP7 is part of the matrilysin family having gelatinase activity, and is frequently expressed in healthy tissues [13].…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

Szentléleky

Szegeczki

Karanyicz

et al. 2019

IJMS

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide also secreted by non-neural cells, including chondrocytes. PACAP signaling is involved in the regulation of chondrogenesis, but little is known about its connection to matrix turnover during cartilage formation and under cellular stress in developing cartilage. We found that the expression and activity of hyaluronidases (Hyals), matrix metalloproteinases (MMP), and aggrecanase were permanent during the course of chondrogenesis in primary chicken micromass cell cultures, although protein levels changed daily, along with moderate and relatively constant enzymatic activity. Next, we investigated whether PACAP influences matrix destructing enzyme activity during oxidative and mechanical stress in chondrogenic cells. Exogenous PACAP lowered Hyals and aggrecanase expression and activity during cellular stress. Expression and activation of the majority of cartilage matrix specific MMPs such as MMP1, MMP7, MMP8, and MMP13, were also decreased by PACAP addition upon oxidative and mechanical stress, while the activity of MMP9 seemed not to be influenced by the neuropeptide. These results suggest that application of PACAP can help to preserve the integrity of the newly synthetized cartilage matrix via signaling mechanisms, which ultimately inhibit the activity of matrix destroying enzymes under cellular stress. It implies the prospect that application of PACAP can ameliorate articular cartilage destruction in joint diseases.

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Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

Szentléleky

Szegeczki

Karanyicz

et al. 2019

IJMS

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“…Antler tissues were collected from 3-year-old health sika deer as growing for about 60 d after casting of the previous hard antler, and performed as described previously. 33 Briefly, the distal 5 cm of growing tip was removed and sectioned sagittally along the longitudinal axis. A part of the tip was then cut into 4-6 mm pieces, flash frozen in liquid nitrogen and stored at ¡70 C for in situ hybridization, and the remaining tip was used for isolation of antler chondrocytes.…”

Section: Tissue Collectionmentioning

confidence: 99%

“…The cartilaginous layer was dissected as described previously. 33 The separated cartilage tissue was further cut into fine pieces (about 1 £ 1 mm). After washing thoroughly with DMEM, the fine pieces were incubated with 0.1% hyaluronidase in D-Hanks for 1h at 38 C. The cartilaginous pieces were then washed twice with Hanks' balanced salt solution (HBSS) and further digested with 0.1% type II collagenase for 6 h at 38 C with shaking.…”

Section: Isolation and Culture Of Antler Chondrocytesmentioning

confidence: 99%

IGF1 regulates RUNX1 expression via IRS1/2: Implications for antler chondrocyte differentiation

et al. 2017

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Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiologic function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ401 abrogated the induction by rIGF1. Simultaneously, IGF1 could stimulate the expression of IHH which was a well-known marker for prehypertrophic chondrocytes. Further analysis evidenced that IGF1 regulated the expression of IRS1/2 whose silencing resulted in a rise of IHH mRNA levels, but the regulation was impeded by PQ401. Knockdown of IRS1 or IRS2 with specific siRNA could greatly enhance rIGF1-induced chondrocyte differentiation and reduce the expression of RUNX1. Extraneous rRUNX1 might rescue the effects of IRS1 or IRS2 siRNA on the differentiation. In antler chondrocytes, IGF1 played a role in modulating the expression of RUNX1 through IGF1R. Moreover, attenuation of RUNX1 expression advanced the differentiation elicited by rIGF1, while administration of rRUNX1 to chondrocytes treated with IGF1 siRNA or PQ401 reduced their differentiation. Additionally, siRNA-mediated downregulation of IRS1 or IRS2 in the chondrocytes impaired the interaction between IGF1 and RUNX1. Collectively, IGF1 could promote the proliferation and differentiation of antler chondrocytes. Furthermore, IRS1/2 might act downstream of IGF1 to regulate chondrocyte differentiation through targeting RUNX1.

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“…This is contrary to the effect of PTHrP. Wang et al found that PTHrP inhibited the expression of MMP-13 in antler chondrocytes [42], whilst other studies observed that the application of PTHrP significantly increased the expression of type II collagen and aggrecan [31].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-15a-5p Regulates the Development of Osteoarthritis by Targeting PTHrP in Chondrocytes

Duan

Huang

et al. 2019

BioMed Research International

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Background and Aims. A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. Methods. Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. Results. The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. Conclusions. miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.

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Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler chondrocytes

Cited by 9 publications

References 28 publications

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures

IGF1 regulates RUNX1 expression via IRS1/2: Implications for antler chondrocyte differentiation

MicroRNA-15a-5p Regulates the Development of Osteoarthritis by Targeting PTHrP in Chondrocytes

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