Cultured Human Periosteal-Derived Cells Have Inducible Adipogenic Activity and Can Also Differentiate Into Osteoblasts in a Perioxisome Proliferator-Activated Receptor-Mediated Fashion

Abstract

We investigated the adipogenic activity of cultured human periosteal-derived cells and studied perioxisome proliferator-activated receptor (PPAR) ligand-mediated differentiation of cultured human periosteal-derived cells into osteoblasts. Periosteal-derived cells expressed adipogenic markers, including CCAAT/enhancer binding protein α (C/EBP- α), C/EBP-δ, aP2, leptin, LPL, and PPARγ. Lipid vesicles were formed in the cytoplasm of periosteal-derived cells. Thus, periosteal-derived cells have potential adipogenic activity. The PPARα and PPARγ agonists, WY14643 and pioglitazone, respectively, did not modulate alkaline phosphatase (ALP) activity in periosteal-derived cells during induced osteoblastic differentiation, however, the PPARα and PPARγ antagonists, GW6471 and T0070907, respectively, both decreased ALP activity in these cells. WY14643 did not affect, whereas pioglitazone enhanced, alizarin red-positive mineralization and calcium content in the periosteal-derived cells. GW6471 and T0070907 both decreased mineralization and calcium content. By RT-PCR, pioglitazone significantly increased ALP expression in periosteal-derived cells between culture day 3 and 2 weeks. Pioglitazone increased Runx2 expression after 3 days, which declined thereafter, but did not alter osteocalcin expression. Both of GW6471 and T0070907 decreased ALP mRNA expression. These results suggest that pioglitazone enhances osteoblastic differentiation of periosteal-derived cells by increasing Runx2 and ALP mRNA expression, and increasing mineralization. GW6471 and T0070907 inhibit osteoblastic differentiation of the periosteal-derived cells by decreasing ALP expression and mineralization in the periosteal-derived cells.In conclusion, although further study will be needed to clarify the mechanisms of PPAR-regulated osteogenesis, our results suggest that PPARγ agonist stimulates osteoblastic differentiation of cultured human periosteal-derived cells and PPARα and PPARγ antagonists inhibit osteoblastic differentiation in these cells.

Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors

“…Dual agonists for PPARɑ/PPARß [ 18 ] and the PPARɑ agonist and peroxisome proliferator fenofibrate [ 83 ] induced osteoblast differentiation. Although PPARɑ knockout mice exhibited no obvious bone phenotype and normal osteoblast differentiation [ 19 ], the PPARɑ antagonist GW6471 inhibited differentiation of periosteal cells into osteoblasts [ 84 ]. Recently, PPARß was recognized as a key regulator of bone turnover inducing osteoblast differentiation by amplification of Wnt -dependent and β-catenin -dependent pathways [ 20 ].…”

Obesity does not affect the healing of femur fractures in mice

“…Wnt/b-catenin signalling prevents apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts [56] and stimulates the osteogenic response [57]. In addition, recent studies indicate that PPARy may not only act adipogenic but also osteogenic [58][59][60]. Thus, the increased PPARy expression, which was associated with an only slight increase of the number of callus adipocytes, may not necessarily result in a deterioration of femur fracture healing.…”

Proteomics Analysis Reveals an Important Role for the PPAR Signaling Pathway in DBDCT-Induced Hepatotoxicity Mechanisms

“…The two groups were both blank control groups. In addition, cells were cultured by adding different concentrations of T0070907 for 12 h (0, 20, 40 and 50 µmol/L) [ 26 , 27 , 28 , 29 , 30 , 31 ] and then adding 4 µmol/L of DBDCT for 24 h.…”