Vernet Dolores, Nolazco Gaby, Cantini Liliana, Magee Thomas R, Qian Ansha, Rajfer Jacob, Gonzalez-Cadavid Nestor F
Department of Urology, UCLA School of Medicine, Los Angeles, California 90095, USA.
Biol Reprod. 2005 Dec;73(6):1199-210. doi: 10.1095/biolreprod.105.041038. Epub 2005 Aug 10.
Tissue ossification in Peyronie disease (commonly known as Peyronie's disease [PD]), a localized fibrotic lesion within the tunica albuginea (TA) of the penis, may result from osteogenic differentiation of fibroblasts, myofibroblasts, and/or adult stem cells in the TA, and may be triggered by chronic inflammation, oxidative stress, and profibrotic factors like transforming growth factor beta 1 (TGFB1). In this study, we have investigated whether cultures of cells from normal TA and PD plaques undergo osteogenesis, express markers for stem cells, and originate other cell lineages via processes modulated by TGFB1. We found that TA and PD cells in osteogenic medium (OM) expressed osteogenic markers, alkaline phosphatase, and osteopontin and underwent calcification. PD cells, but not TA cells, formed foci in soft agar that were positive for alkaline phosphatase and calcification and expressed the mRNAs for osteoblast-specific factors pleiotrophin and periostin and bone morphogenic protein 2. Both cultures expressed stem cell marker CD34 antigen but not protein tyrosine phosphatase, receptor type c. TA and PD cells expressed smooth-muscle cell markers smoothelin and transgelin. None of the cultures underwent adipogenesis in adipogenic medium. Incubation with TGFB1 increased osteogenesis and myofibroblast differentiation and reduced CD34 antigen expression in both cultures. TA and PD cells modulated the differentiation of the multipotent C3H 10T(1/2) cells in dual cultures, into osteoblasts and myofibroblasts. In conclusion, both TA and PD cultures contain cells, presumably stem cells, that undergo osteogenic and myofibroblast differentiation, and may induce these processes by paracrine interactions. This may explain progression of fibrosis in the PD plaque and its eventual calcification.
佩罗尼氏病（通常称为佩罗尼氏病[PD]）中的组织骨化是阴茎白膜（TA）内的局部纤维化病变，可能源于TA中成纤维细胞、肌成纤维细胞和/或成体干细胞的成骨分化，并且可能由慢性炎症、氧化应激以及诸如转化生长因子β1（TGFB1）等促纤维化因子触发。在本研究中，我们调查了来自正常TA和PD斑块的细胞培养物是否经历成骨作用、表达干细胞标志物以及通过TGFB1调节的过程产生其他细胞谱系。我们发现，在成骨培养基（OM）中的TA和PD细胞表达成骨标志物、碱性磷酸酶和骨桥蛋白并发生钙化。PD细胞而非TA细胞在软琼脂中形成碱性磷酸酶和钙化呈阳性且表达成骨细胞特异性因子多效蛋白和骨膜蛋白以及骨形态发生蛋白2的mRNA的病灶。两种培养物均表达干细胞标志物CD34抗原，但不表达蛋白酪氨酸磷酸酶受体型c。TA和PD细胞表达平滑肌细胞标志物平滑肌肌动蛋白和原肌球蛋白。在成脂培养基中，没有一种培养物发生脂肪生成。用TGFB1孵育可增加两种培养物中的成骨作用和肌成纤维细胞分化，并降低CD34抗原表达。TA和PD细胞在共培养中调节多能C3H 10T(1/2)细胞向成骨细胞和肌成纤维细胞的分化。总之，TA和PD培养物均含有可能是干细胞的细胞，这些细胞经历成骨和肌成纤维细胞分化，并可能通过旁分泌相互作用诱导这些过程。这可能解释了PD斑块中纤维化的进展及其最终钙化。
