Defective Osteogenic Differentiation in the Development of Osteosarcoma

Table 1

Summary of some currently used differentiation agents in human osteosarcoma cells. These differentiation agents are in general nonspecific differentiation-promoting agents, and are able to promote osteogenic differentiation in mesenchymal stem cells. These agents can inhibit the proliferation and induce apoptosis in OS cells.

Class	Target	Ligand	Possible mechanism	References
	PPARy	Troglitazone	(i) Increased susceptibility to apoptosis	Haydon 2007, Logan 2004 [15, 146]
		Ciglitazone	(ii) Decreased proliferative capacity	Scotlandi 1996 [54]
		Pioglitazone	(iii) Increased differentiation (ALP Activity)	Deng 2008 [58]
Nuclear		9 cis-retinoic acid	(i) Induced morphologic differentiation	Haydon 2002, Logan 2004 [15, 146]
receptor	Retinoids		(ii) Inhibited anchorage-dependent growth	Luu 2004 [143]
ligands		All-trans retinoic acid	(iii) Decreased proliferative capacity
	Estrogens	Tamoxifen	(i) Increased apoptosis	Hoang 2004 [149]
		Raloxifene	(ii) Decreased cell proliferation
		17-β Estradiol	(iii) Increased osteoblastic differentiation markers
	Vitamin D	1,25-dihydroxyvitamin D3	(i) Decreased cell proliferation (increased p21 expression causing G1 arrest)	Cadigan 1997 [144]
				Wodarz 1998 [145]
			(ii) Increased differentiation (ALP, OCN)
			(iii) Increased apoptosis
	Parathyroid	Parathyroid	Increased differentiation via MAPK	Iwaya 2003 [148]
Hormone (s)	hormone	Hormone-related	pathway (ALP, Type 1 Collagen)
		peptide (PTHrP)
		BMP2	(i) −Runx2: increased cell proliferation, no differentiation in OS cells	Reya 2001 [63]
	Bone	BMP4
Growth	morphogenetic	BMP6	(ii) +Runx2: decreased cell proliferation, increased OS cell differentiation
factors	proteins	BMP9