Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Table 1 Effects of various antimicrobial agents on osteogenic differentiation

Agent		Ref.	Cell / animal	Effect	Concentration
Antituberculosis drugs	Rifampicin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
		[15]	BMSCs	Inhibition	4-128 μg/mL
β-lactams	Penicillin	[16]	BMSCs	No effect	30 μg/mL
		[14]	Osteoblasts	Inhibition	≥ 500 μg/mL
	Flucloxacillin	[16]	BMSCs	No effect	200 μg/mL
	Nafcillin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
	Cefazolin	[14]	Osteoblasts	Inhibition	≥ 200 μg/mL
	Cefuroxime	[16]	BMSCs	No effect	50 μg/mL
	Cefotaxime	[14]	Osteoblasts	Inhibition	≥ 500 μg/mL
	Cefepime	[14]	Osteoblasts	Inhibition	≥ 200 μg/mL
	Imipenem	[14]	Osteoblasts	No effect	0-1000 μg/mL
	Meropenem	[14]	Osteoblasts	Inhibition	≥ 500 μg/mL
Macrolides	Azithromycin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
Aminoglycosides	Gentamicin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
		[16]	BMSCs	Inhibition	≥ 75 μg/mL
		[17]	BMSCs	Inhibition	50-200 μg/mL
		[18]	C2C12	Inhibition	12.5-800 μg/mL
	Amikacin	[14]	Osteoblasts	No effect	0-1000 μg/mL
	Tobramycin	[20]	BMSCs	Inhibition	300-1000 μg/mL
		[14]	Osteoblasts	Inhibition	≥ 500 μg/mL
Tetracyclines	Tetracycline	[22]	BMSCs	Inhibition	10 μg/mL
	Doxycycline	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
	Minocycline	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
Quinolones	Levofloxacin	[14]	Osteoblasts	Inhibition	≥ 200 μg/mL
	Ciprofloxacin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
Polypeptide antibiotics	Colistin	[14]	Osteoblasts	Inhibition	≥ 100 μg/mL
	Bacitracin	[23]	BMSCs	Promotion	0.1-10 μmol/L
	Vancomycin	[24]	BMSCs	No effect	0-500 μg/mL
		[24]	BMSCs	Inhibition	5000 μg/mL
		[14]	Osteoblasts	No effect	0-2000 μg/mL
		[25]	BMSCs	No effect	0-20 μg/mL
		[16]	BMSCs	Inhibition	200 μg/mL
Other types of antibiotics	Metronidazole	[16]	BMSCs	No effect	20 μg/mL
	Trimethoprim	[14]	Osteoblasts	Inhibition	≥ 500 μg/mL
	Linezolidone	[14]	Osteoblasts	Inhibition	≥100 μg/mL
	Salinomycin	[26]	BMSCs	No effect	10 μmol/L
Natural peptides	Lactoferrin	[27]	Adipose-derived stem cells	Promotion	10-100 μg/mL
		[29]	MC3T3-E1	Promotion	1-1000 μg/mL
	Hepcidin	[30]	BMSCs	Promotion	0.2 mmol/L
	LL-37	[31]	BMSCs	Promotion	5-20 μg/mL
	KR-12	[32]	BMSCs	Promotion	1-1000 μg/mL
Chinese traditional drug extracts	Cordycepin	[33]	Adipose-derived stem cells	Promotion	10 μg/mL
		[34]	BMSCs	Promotion	10 μg/mL
	Tanshinone IIA	[35]	BMSCs	Promotion	1-5 μmol/L
		[36]	C2C12	Promotion	2.5-10 μmol/L
	Andrographolide	[37]	Osteoblasts	Promotion	4.46 or 8.92 μmol/L
	Baicalin	[38]	Sprague-Dawley rats	Promotion	50 mg/kg
		[39]	Osteoblasts	Promotion	50 μmol/L
	Costunolide	[40]	C3H10T1/2	Promotion	1 ng/mL
	Extract of lithospermum	[41]	C2C12	Promotion	30 or 60 μg/mL
		[42]	C2C12	Promotion	2 or 4 μg/mL
	Naringin	[43]	Adipose-derived stem cells	Promotion	0.1 μmol/L
	Curcumin	[44]	Adipose-derived stem cells	Promotion	5-20 μmol/L
	Limonene	[45]	C2C12	Promotion	2.5-10 μL
	Extract of piperaceae	[46]	Sprague-Dawley rats	Promotion	100 or 200 mg/kg
	Eugenol	[47]	Dental pulp cells	Inhibition	0.1-1 mL
	Saikosaponin-A	[48]	BMSCs	Promotion	10-40 μL
	Licochalcone A	[49]	MC3T3-E1	Promotion	2.5-5 μL
Antifungal drugs	Trichostatin A	[50]	Adipose-derived stem cells	Promotion	75 nL
		[51]	Periodontal ligament cells	Promotion	100-400 nL
		[52]	Adipose-derived stem cells	Promotion	1 μL
	Voriconazole	[53]	Osteoblasts	Promotion	15 or 200 μg/mL
	Fluconazole	[53]	Osteoblasts	No effect	15 or 200 μg/mL

Table 2 Effects of various antimicrobial agents on chondrogenic differentiation

Agent		Ref.	Cell	Effect	Concentration
Antibiotics	Doxycycline	[57]	MSCs	Promotion	2 μg/mL
	Oxytetracycline	[58]	ATDC5	Promotion	0.01-10 μmol/L
	PMA	[61]	Embryonic stem cells	Inhibition	0.1 μmol/L
Natural peptides	Lactoferrin	[60]	ATDC5	Promotion	1 μmol/L
Chinese traditional drug extracts	Cordycepin	[59]	MSCs	Promotion	1 μg/mL
Antifungal drugs	Trichostatin A	[62]	BMSCs	Inhibition	100 nmol/L

Table 3 Effects of various antimicrobial agents on adipogenic differentiation

Agent		Ref.	Cell / animal	Effect	Concentration
Antibiotics	Isoniazid	[67]	3T3-L1	Inhibition	0.5-10 mmol/L
		[67]	Adipose stem cells	Inhibition	2 or 10 mmol/L
	Streptomycin	[68]	BMSCs	Inhibition	100 μg/mL
	Spiramycin	[69]	3T3-L1	Inhibition	2.5-20 μmol/L
	Salinomycin	[26]	BMSCs	No effect	10 μmol/L
	Geldanamycin	[70]	3T3-L1	Inhibition	0.001-1 μmol/L
Natural peptides	Lactoferrin	[71]	MC3T3-G2/PA6	Inhibition	10-100 μg/mL
		[72]	C1C12	Inhibition	0.1-10 μmol/L
		[73]	Subcutaneous preadipocytes	Promotion	10 μmol/L
Chinese traditional drug extracts	Cordycepin	[74]	3T3-L1	Inhibition	10-100 μg/mL
	Tanshinone IIA	[75]	3T3-L1	Inhibition	2.5-10 μmol/L
		[76]	3T3-L1	Inhibition	1-10 μmol/L
	Andrographolide	[77]	3T3-L1	Inhibition	1-5 μg/mL
	Baicalin	[78]	3T3-L1	Inhibition	200 μmol/L
		[79]	Atherosclerosis mice	Inhibition	50 or 100 mg/kg
	Oleuropein	[80]	BMSCs	Inhibition	10 μmol/L
		[81]	3T3-L1	Inhibition	0.1-100 μmol/L
	Piperlonguminine	[82]	3T3-L1	Promotion	3-30 μmol/L
	Hydroxytyrosol	[83]	BMSCs	Promotion	1 or 100 mmol
		[84]	Omental pre-adipocyte cells	Inhibition	30 μg/mL
	Shikonin	[85]	3T3-L1	Inhibition	0.5-2 μmol/L
	Ursolic acid	[86]	3T3-L1	Inhibition	2.5-10 μmol/L
	Alpinia officinarum	[87]	3T3-L1	Inhibition	150-400 μg/mL
	Dioscin	[88]	3T3-L1	Inhibition	1-4 μmol/L
	Methyl cinnamate	[89]	3T3-L1	Inhibition	12.5-100 μmol/L
	Tetrandrine	[90]	3T3-L1	Inhibition	2.5-10 μmol/L
	Honokiol	[91]	3T3-L1	No effect	1-10 μmol/L
	Licochalcone A	[92]	3T3-L1	Inhibition	5 or 10 μmol/L
Antifungal drugs	Trichostatin A	[51]	Periodontal ligament cells	No effect	400 nmol/L
		[93]	3T3-L1	Inhibition	500 nmol/L
Antiviral drugs	Efavirenz	[94]	Pre-adipocytes	Inhibition	0.5-4 μmol/L
		[104]	SGBS pre-adipocytes	Inhibition	0.1-5 μmol/L
	Zidovudine	[95]	3T3-F442A	Inhibition	6-50 μmol/L
		[99]	3T3-F442A	Inhibition	1-6 μmol/L
	Stavudine	[95]	3T3-F442A	Inhibition	3-75 μmol/L
	Lamivudine	[95]	3T3-F442A	Inhibition	8-200 μmol/L
	Nelfinavir	[98]	3T3-L1	Inhibition	20 μmol/L
	Efavirenz	[96]	Adipocyte precursor cells	Inhibition	4 μmol/L
		[97]	Adipocyte precursor cells	Inhibition	2 or 4 μmol/L
	Maraviroc	[96]	Adipocyte precursor cells	No effect	0.1-4 μmol/L
	Nevirapine	[97]	Adipocyte precursor cells	Promotion	2 or 4 μmol/L
	Darunavir	[100]	3T3-L1	Inhibition	0.1-25 μmol/L
	Raltegravir	[101]	3T3-F442A	Inhibition	1-50 μg/mL
	Indinavir	[102]	3T3-L1 and 3T3-F442A	Inhibition	10 or 20 μmol/L
		[103]	3T3-F442A	Inhibition	1-50 μg/mL
	Elvitegravir	[104]	SGBS pre-adipocytes	Inhibition	0.1-5 μmol/L
Antimalarials	Amodiaquine	[105]	3T3-L1	Inhibition	0.1-10 μmol/L
	Quinine	[106]	Preadipocytes	Promotion	5-50 μmol/L
	Artemisinic Acid	[107]	Adipose-derived stem cells	Inhibition	50 or 200 μmol/L