scholarly journals The Contributive Role of IGFBP-3 and Mitochondria in Synoviocyte-Induced Osteoarthritis through Hypoxia/Reoxygenation Injury: A Pathogenesis-Focused Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Daniel Gululi ◽  
Guy-Armel Bounda ◽  
Jianping Li ◽  
Haohuan Li
Keyword(s):  
Growth Factor ◽  
Essential Role ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Insulin Like Growth Factor ◽  
Synovial Joint ◽  
Hypoxia Inducible Factors ◽  
Igfbp 3 ◽  
Hypoxia Reoxygenation

Osteoarthritis (OA), one of the most common joint disorders, is characterized by chronic progressive cartilage degradation, osteophyte formation, and synovial inflammation. OA lesions are not only located in articular cartilage but also in the entire synovial joint. Nevertheless, most of the early studies done mostly focused on the important role of chondrocyte apoptosis and cartilage degeneration in the pathogenesis and progress of OA. The increased expression of hypoxia-inducible factors (HIF-1α and HIF-2α) is known to be the cellular and biochemical signal that mediates the response of chondrocytes to hypoxia. The role of the synovium in OA pathogenesis had been poorly evaluated. Being sensitive to hypoxia/reoxygeneration (H/R) injury, fibroblast-like synoviocytes (FLS) play an essential role in cartilage degradation during the course of this pathology. Insulin-like growth factor binding protein 3 (IGFBP-3) acts as the main carrier of insulin-like growth factor I (IGF-I) in the circulation and remains the most abundant among the six IGFBPs. Synovial fluids of OA patients have markedly increased levels of IGFBP-3. We aim to discuss the interconnected behavior of IGFBP-3 and synoviocytes during the course of osteoarthritis pathogenesis, especially under the influence of hypoxia-inducible factors. In this review, we present information related to the essential role that is played by IGFBP-3 and mitochondria in synoviocyte-induced osteoarthritis through H/R injury. Little research has been done in this area. However, strong evidences show that the level of IGFBP-3 in synovial fluid significantly increased in OA, inhibiting the binding of IGF-1 to IGFR 1 (IGF receptor-1) and therefore the inhibition of cell proliferation. To the best of our knowledge, this is the first paper providing a comprehensive explanatory contribution of IGFBP-3 and mitochondria in synovial cell-induced osteoarthritis through hypoxia/reoxygenation mechanism.

scholarly journals Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors

Oncogene ◽  
2016 ◽  
Vol 35 (42) ◽  
pp. 5515-5526 ◽  
Author(s):  
S-C Lee ◽  
H-Y Min ◽  
H J Jung ◽  
K H Park ◽  
S Y Hyun ◽  
...  
Keyword(s):  
Growth Factor ◽  
Histone Deacetylase ◽  
Essential Role ◽  
Histone Deacetylase Inhibitors ◽  
Insulin Like Growth Factor

scholarly journals Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression

2008 ◽  
Vol 28 (7) ◽  
pp. 2460-2469 ◽  
Author(s):  
Lan Liao ◽  
Xian Chen ◽  
Shu Wang ◽  
Albert F. Parlow ◽  
Jianming Xu
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Steroid Receptor Coactivator ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator for nuclear receptors including vitamin D receptor (VDR). Growth hormone (GH) regulates insulin-like growth factor I (IGF-I) expression, and IGF-I forms complexes with acid-labile subunit (ALS) and IGF-binding protein 3 (IGFBP-3) to maintain its circulating concentration and endocrine function. This study demonstrated that the circulating IGF-I was significantly reduced in SRC-3−/− mice with the C57BL/6J background. However, SRC-3 deficiency affected neither GH nor ALS expression. The low IGF-I level in SRC-3−/− mice was not due to the failure of IGF-I mRNA and protein synthesis but was a consequence of rapid degradation. The rapid IGF-I degradation was associated with drastically reduced IGFBP-3 levels. Because IGF-I and IGFBP-3 stabilize each other, SRC-3−/− mice were crossbred with the liver-specific transthyretin (TTR)-IGF-I transgenic mice to assess the relationship between reduced IGF-I and IGFBP-3. In SRC-3−/−/TTR-IGF-I mice, the IGF-I level was significantly increased over that in SRC-3−/− mice, but the IGFBP-3 level failed to increase proportionally, indicating that the low IGFBP-3 level is a responsible factor that limits the IGF-I level in SRC-3−/− mice. Furthermore, IGFBP-3 mRNA was reduced in SRC-3−/− mice. The IGFBP-3 promoter activity induced by vitamin D, through VDR, was diminished in SRC-3−/− cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene. In agreement with the role of SRC-3 in VDR function, the expression of several VDR target genes was also reduced in SRC-3−/− mice. Therefore, SRC-3 maintains IGF-I in the circulation through enhancing VDR-regulated IGFBP-3 expression.

scholarly journals Insulin-like growth factor-1 in articular cartilage repair for osteoarthritis treatment

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Caining Wen ◽  
Limei Xu ◽  
Xiao Xu ◽  
Daping Wang ◽  
Yujie Liang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Repair ◽  
Critical Issue ◽  
Delivery Systems ◽  
Chondrocyte Apoptosis ◽  
Insulin Like Growth Factor ◽  
Articular Cartilage Repair ◽  
Osteoarthritis Treatment

AbstractArticular cartilage repair is a critical issue in osteoarthritis (OA) treatment. The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. Here, we reviewed the role of IGF-1 in cartilage anabolism and catabolism. Moreover, we discussed the potential role of IGF-1 in OA treatment. Of note, we summarized the recent progress on IGF delivery systems. Optimization of IGF delivery systems will facilitate treatment application in cartilage repair and improve OA treatment efficacy.

The proteolysis of insulin-like growth factor binding proteins in ovine uterine luminal fluid

1998 ◽  
Vol 10 (4) ◽  
pp. 309 ◽  
Author(s):  
A. J. Peterson ◽  
A. M. Ledgard ◽  
S. C. Hodgkinson
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Prolonged Exposure ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Late Luteal Phase ◽  
Reduced Activity ◽  
Igfbp 3

During days 12–15 after oestrus (day 0), the uterine luminal fluid (ULF) of both pregnant and non-pregnant ewes contains only two prominent insulin-like growth factor binding proteins (IGFBPs) of 16–18 kDa and 22–24 kDa which preferentially bind IGF-2. Immunoblotting with an IGFBP-3 antibody revealed these to be proteolytic fragments of IGFBP-3. In contrast, the ULF from anoestrus and ovariec-tomized ewes contained intact IGFBP-3 (40–44 kDa) and IGFBP-2 (34 kDa). Co-incubation of ULF from an anoestrus ewe with that from a day 12 cycling ewe cleaved the IGFBP-3 present into the two lower molec-ular weight IGFBPs characteristic of ewes in the late luteal phase of the oestrous cycle. The variation in pro-teolytic activity both during the year and during the cycle suggested an influence of progesterone. Supplementation of progesterone to long-term ovariectomized ewes via a CIDR-G™ breeding device for 5, 10 or 15 days induced marked proteolytic activity in all 10-day treated sheep. The ULF from the 15-day treated ewes showed reduced activity and could inhibit the activity present in 10-day ULF, suggesting the induction of an inhibitor after prolonged exposure to progesterone treatment. A possible role of IGFBP-3 proteolysis in the ovine ULF may be to selectively increase the bioavailability of IGF-1 in the uterine microenvironment, which may be crucial for the rapid elongation of trophoblast that begins during days 12–15 after mating.

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