Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans
Abstract
:1. Introduction
2. Overview of the Literature Data
3. Effects of GCs on PG Expression and GAG Content in Normal Tissues and Cells
3.1. Cartilage and Chondrocytes
3.2. Lungs and Fibroblasts
3.3. Dermal Fibroblasts
3.4. Osteoblasts and Bone Marrow Stromal Cells
3.5. Other Tissues and Cells
4. Effects of GCs on PG Expression and GAG Content in Malignant Tissues and Cells
5. Effects of GCs on PG Expression and GAG Content in Normal and Malignant Brain Tissues and Cells
5.1. Brain ECM
5.2. Effects of GCs on Normal Brain PGs and GAGs
5.3. Effects of Glucocorticoids on PGs and GAGs in Gliomas
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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GC | Dose, Regimen | Tissue/Cell/Animal | Detection | Changes in PGs and GAGs | Ref. |
---|---|---|---|---|---|
Cartilage and Chondrocytes | |||||
DXM | 2.5 mg/kg for five cycles (5 consecutive days with breaks of 16 days) | Wistar rats | 6 months | Total GAGs (↗); sulfated GAGs in TMZ-treated animals (↘) | [39] |
125 μg/kg from gestation day 20 until parturition | Pregnant spiny mice | Offspring | Total PGs in articular and growth cartilages in the offspring (↘) | [44] | |
0.2., 0.8, and 1.2 mg/kg once a day from day 12 to day 17 of gestation | Pregnant C57BL/6 mice | Offspring | Gene and protein expression of aggrecan in offspring (↘) | [45] | |
1 mg/kg | Rats | Prevented TNFα-induced degradation of aggrecan | [38] | ||
100 nM and higher | Bovine and human cartilage explants | 6 days | Prevented TNFα-induced GAG and PG loss | [36] | |
100 nM | Human osteochondral explants | 21 days | Prevented a loss of sulfated GAGs from injury- and cytokine-treated explants | [48] | |
10−6, 10−7, and 10−8 M | Chondrocytes isolated from mouse knee joints | 24 h | Total PG content (↘) | [42] | |
1 µM | Primary bovine articular chondrocytes Chondrogenically differentiated mesenchymal stem cells | Day 21, day 14, and days 21–35 | GAG production (↗) | [46] | |
50–150 μM | Human chondrocytes from knee joints | 1–7 days | Aggrecan (↘) | [43] | |
DXM triamcinolone prednisolone | 10−10 to 10−4 M | Primary equine articular chondrocytes from foals, as well as 7-year-old and adult horses | 24 h | Biglycan (=) Decorin (=) | [47] |
Prednisolone | 0.5–1 mg/kg/day for 6 months and 13 months | Gottingen miniature pigs | 6 months 13 months | No change; GAG content (↘) | [33] |
Methylprednisolone acetate | 80 mg/mL, 4 injections | Suffolk cross sheep | 20 weeks | PG content (↘) | [35] |
0.05 and 0.5 mg/mL | Articular cartilage from1–10-year-old horses | Total PGs (↘) | [41] | ||
Betamethasone | Californian rabbits | 1–5 weeks 6–8 weeks | No change; total PG content (↘) | [34] | |
Triamcinolone acetonide | 1.25, 2.5, and 5 mg/mL | Canine cartilage explant | PG content (↘) | [40] | |
0.11 mg/mL | Primary canine normal chondrocytes Osteoarthritic chondrocytes | Aggrecan (↘) Aggrecan (↗) | [40] | ||
Cortisone | Rats | 1 and 4 weeks | Restored osteoarthritis-induced decrease in total GAG content | [37] | |
Lung and Fibroblasts | |||||
DXM | 20 nM | C57Bl/6J mice | 24 h | Betaglycan at mRNA and protein levels (↗) | [49] |
DXM, methylprednisolone, budesonide, and fluticasone | Mouse fibroblasts | Betaglycan (↗) | [49] | ||
Cortisol | 1.5–4 mg/day | Fetal sheep lung | 9 days | Chondrotin-6-sulfate (↘); Versican (=); chondroitin-4-sulfate (=) | [50] |
Betamethasone | 11.4 mg | Fetal sheep lung | 24 h and 36 h | Versican (↘); chondrotin-6-sulfate (↘); chondroitin-4-sulfate (↘) | [50] |
Budesonide | 10−8 M | Human lung fibroblasts | 24 h | Serum-induced total PG increase (↘); Decorin (↘); Versican (↘) | [51] |
Dermal Fibroblasts | |||||
DXM | 1µM | Human skin fibroblasts | Decorin at mRNA and protein levels (↗); Biglycan (=); the length of CS/DS chains attached to Decorin and Biglycan core proteins (=); prevented TGFβ-induced downregulation of Decorin and upregulation of Biglycan | [52] | |
1 µM | Human skin fibroblasts MG-63 osteoblast-like osteosarcoma cell line | 1–2 h | Hyaluronan synthase 2 (HAS2) (↘) | [53] | |
Fluocinolone acetonide, budesonide, and hydrocortisone | 10−11–10−5 M | Human skin fibroblasts | Accumulation of hyaluronic acid (HA) (↘); DS content (↘) in the culture medium on the cell surface and in the cells; decrease in HS content (↘) in culture medium but not on cell surface; considerably less effect | [54] | |
Osteoblasts and Bone Marrow Stromal Cells | |||||
DXM | 10−10–10−7 M | Human osteoblasts (HOBs) and adult human bone marrow stromal cells (BMSC) | 7 days | Decorin at mRNA and protein levels (↗); Biglycan at mRNA and protein levels (↘) in both the conditioned medium and the cell layer | [55] |
10−10–10−7 M | Osteoblast-like and preosteoblast-like cell lines (murine MC3T3-E1 and rat RCT1) | 9–48 h | Betaglycan (↗) | [56] | |
10−10–10−7 M | Immature, non-transformed mouse bone-marrow-derived mast cells (mBMMCs) | 9–48 h | Serglycin (↗) | [56] | |
0.2 mg/kg once a day from gestational day 9 to 20 | Rats | Total PG content (↘) in the growth plate | [57] | ||
100 nM | Young bovine bone marrow stromal cells (BMSCs) seeded on agarose hydrogels | PG biosynthesis (↗) | [58] | ||
100 nM | Young bovine bone marrow stromal cells (BMSCs) seeded on peptide scaffolds | PG accumulation (↘) | [58] | ||
Hydrocortisone | 1 μM | D2XRII, Bl6, and 14F1 bone marrow stromal cell lines | HSPG synthesis (↘) in all three cell lines; altered pattern of CS/DSPGs in the culture media by DS1 and DS3 (↗) DS2 (↘) | [59] | |
Brain | |||||
DXM | 1 mg/kg 2.5 and 5 mg/kg | Wistar rats | 24 h | PG expression (=); overall transcriptional activity of PGs (↗); syndecan-1 (↗); glypican-1 (↗); brevican (↗); CSPG4/NG2 (↗); Lumican (↗); Decorin (↘); CS content in hippocampus (↗); CS content in cortex (↘); HS content (↘) in both | [60] |
1 mg/kg | SCID mice | Glypican-1 (↗); syndecan-1 (↗); Versican (↗); CS content (↘) in the subcortex; Biglycan in cortex (↗) | [61] | ||
5 mg/kg once daily for 6 consecutive weeks | Adult mice | Agrin (↘) | [62] | ||
100 μg DEX in 20 μL nitrocellulose Local delivery into rat brain | Rats | 7 days | CS content (↘) | [63] | |
0.01–0.5 μM 50–200 μM | Rat organotypic hippocampal cultures | Glypican-1 (↗); Versican (↗); syndecan-1 (↘); Biglycan (↘) | [60] | ||
Methylprednisolone | 30 mg/kg body weight intravenously immediately after SCI surgery | Female Long–Evans rats (acute spinal cord injury model) | 24 h | Neurocan (↘) | [64] |
Pretreatment 10 and 50 μM | AMPA + cyclothiazide-induced reactivated primary cultured astrocytes (Sprague–Dawley rats) | Neurocan (↘) Phosphacan (↘) | [64] | ||
Other Tissue and Cells | |||||
DXM | 16 mg | Patients undergoing colorectal, pancreas, or liver surgery | Postoperative day 1 | Plasma syndecan-1 level (=); heparan sulfate content (↘) | [65] |
0.55 μM | Human eyes in ex vivo perfusion organ culture | 7 days and 14–21 days after treatment | No change In total GAG (CS, DS, HS, and HA) content in human trabecular meshwork (↗) | [66] | |
Rat mesangial cells (RMCs) and human mesangial cells (HMCs) | Total CS/DSPGs synthesis and secretion (↘); Decorin (↘) Biglycan (↗) | [67] | |||
DXM, hydrocortisone Aldosterone | 200 or 400 ng/mL 200 ng/mL 500 ng/mL | Hepatic stellate cells (HSCs) | Betaglycan mRNA level (↗) | [68] | |
DXM triamcinolone | 1 μM 1 μM | Primary cultures of human tenocytes from explants of healthy human patellar tendon | Total PG content (↘) | [69] | |
Methylprednisolone | New Zealand Black/White F1 mice | Onset of murine lupus nephritis (5 months of age) | Expression, distribution, and intensity of HSPG staining in renal cortex (↘) | [70] | |
2 mg/kg single preoperative dose | Patients undergoing gastrointestinal surgery | 1 and 3 days after surgery | Syndecan-1 (↘); HS content (↘) in endothelial glycocalyx | [71] |
GC | Dose | Tissue/Cells/Animals | Detection | Changes in PGs and GAGs | Ref. |
---|---|---|---|---|---|
DXM | Up to 10−6 M | MCF-7 breast cancer cells | 72 h | mRNA and membrane-bound form of syndecan-1 (↗); concentration of the soluble form of syndecan-1 (=) | [79] |
0.25 µM | Subconfluent A549 cells | 72 h | Heparan sulfate (↗); hyaluronic acid (↗) | [80] | |
100 nmol/L | Bladder cancer cells | 48 h | CD44 expression (↘) | [81] | |
10−7 mol/L | HO-8910 and SKOV-3 human ovarian cancer cells | 6–48 h | CD44 protein level (=); hyaluronic acid secretion (=) | [82] | |
DXM methylprednisolone | 25 μM | Primary cultures of human gliomas (mainly anaplastic astrocytomas) | Total GAG content (↗); both in the cell medium and pronase digest of the cells’ total GAG content: in the culture medium (↘); in the protease cell digest (↗) | [83] |
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Strokotova, A.V.; Grigorieva, E.V. Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans. Int. J. Mol. Sci. 2022, 23, 15678. https://doi.org/10.3390/ijms232415678
Strokotova AV, Grigorieva EV. Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans. International Journal of Molecular Sciences. 2022; 23(24):15678. https://doi.org/10.3390/ijms232415678
Chicago/Turabian StyleStrokotova, Anastasia V., and Elvira V. Grigorieva. 2022. "Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans" International Journal of Molecular Sciences 23, no. 24: 15678. https://doi.org/10.3390/ijms232415678