Cultured human periosteal-derived cells have inducible adipogenic activity and can also differentiate into osteoblasts in a perioxisome proliferator-activated receptor-mediated fashion.

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.

Adipose-derived stem cells on the healing of ischemic colitis: a therapeutic effect by angiogenesis.

BACKGROUND: There has been no specific treatment for ischemic colitis. We verified the effects of adipose-derived stem cells (ASCs) on ischemia-induced colitis in a rat model. METHODS: Forty male Sprague-Dawley rats (10 weeks old; weight, 350 ± 20 g) were divided into two groups: a control group (only fibrinogen and thrombin injected, n = 20) and an ASC group (local implantation of ASCs mixed with thrombin and fibrinogen, n = 20). An ischemic colitis model was established by modifying Nagahata's methods with double-blind randomization. ASCs (1 × 10(6) cells) were implanted intramurally into the ischemic area using a fibrin glue mixture. The severity of adhesion, degree of ileus, the number and size of the ulcers, Wallace macroscopic and microscopic scores, and microvascular density were measured. RESULTS: The degree of ileus was significantly lower, and significantly fewer and smaller ulcerations were found in the ASC group than those in the control group. Wallace macroscopic and microscopic scores were lower in the ASC group than in the control group (1.90 ± 1.22 versus 3.25 ± 1.83, p < 0.01 and 1.55 ± 1.88 versus 2.84 ± 1.89, p < 0.05, respectively). Microvascular density was higher in the ASC group than in the control (54.45 ± 19.45 versus 26.54 ± 13.14, p < 0.01, respectively). CONCLUSIONS: Local implantation of ASCs into an ischemic-injured colonic wall reduced the grade of ischemic injury and enhanced tissue healing by promoting angiogenesis.

[Expressions and clinical significances of c-met, c-erbB-2, COX-2, and IL-6 in the biliary tract cancers].

BACKGROUND/AIMS: c-met, c-erbB-2, interleukin (IL)-6, and cyclooxygenase (COX)-2 expressions are considered to be implicated in the carcinogenesis and progression of cholangiocarcinoma, but the molecular pathogenesis of cholangiocarcinoma is still poorly understood. We aimed to analyze the expressions of each marker and their relationships with clinicopathologic factors. METHODS: One hundred and fourteen tissue samples were obtained from surgically resected specimens from patients with biliary tract cancer. The expressions of c-met, c-erbB-2, COX-2, and IL-6 were examined by immunohistochemically. The expression of each marker and correlations between these markers and clinicopathologic factors were analyzed. RESULTS: The expression rates of each maker were as follows: c-met 34/112 (30.4%), c-erbB-2 5/112 (4.5%), COX-2 53/113 (46.9%), and IL-6 68/113 (60.2%), respectively. c-met expression was more frequently observed in cases with invasion through the adjacent connective tissues (p=0.0263). IL-6 overexpression was more frequently observed in cases with absent lymph node metastasis (p=0.0325). Either c-erbB-2 expression or COX-2 expression was significantly associated with lymph node metastasis (p=0.0442). CONCLUSIONS: The expression of c-met was closely related to the invasiveness of cholangiocarcinoma. Co-expression of c-met, COX-2 and, IL-6 showed a significant correlation with invasiveness and lymph node metastasis and these could be useful marker to guide clinical outcome in patients with cholangiocarcinoma.