Table 1.

Effects of glucocorticoids on PG expression and GAG content in normal tissues and cells. Arrows correspond to upregulation (↗) or downregulation (↘) of the PG core protein expression or total PG/GAG content; (=)—no change in the studied parameters; DXM—dexamethasone.

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]