title: rhPDGF-BB via ERK pathway osteogenesis and adipogenesis balancing in ADSCs for critical-sized calvarial defect repair.
abstract: Adipose-derived stem cells (ADSCs) with the capacity of differentiating into osteo-like cells have been widely investigated for bone tissue engineering as a novel seed cell source. Recombinant human platelet-derived growth factor (rhPDGF-BB) is a clinically proven growth factor with the potential of promoting cell proliferation and osteogenic differentiation during the bone regeneration process. In this study, we investigated the effects of rhPDGF-BB on the proliferation and osteogenic and adipogenic differentiation of rat ADSCs and explored whether the extracellular signal-related kinase (ERK) signaling pathway might be involved. We found that rhPDGF-BB significantly enhanced ADSCs proliferation and osteogenic differentiation, as detected by MTT, real-time polymerase chain reaction (PCR), ALP activity assays, and calcium deposition in vitro, in concert with ERK pathway activation. In contrast, the adipogenesis of ADSCs, as detected by real-time PCR and Oil Red O staining, was suppressed in the presence of rhPDGF-BB. Furthermore, with the supplement of the ERK inhibitor PD98059, cell proliferation and osteogenesis were reduced; as expected, adipogenesis was enhanced. Subsequently, for the first time, we evaluated the effect of ADSCs associated with rhPDGF-BB on bone regeneration in a critical-sized rat calvarial defect model with silk scaffold as a carrier. Micro-computed tomography and histological analyses exhibited dramatically more new bone formation and trabecular number in the Silk/PDGF/ADSC group. These data indicated that rhPDGF-BB promoted cell proliferation and osteogenic differentiation and suppressed adipogenic differentiation in vitro via ERK pathway and that ADSCs associated with rhPDGF-BB could be a promising tissue-engineered construct for craniofacial bone regeneration in vivo.
authors.affiliation: 1 Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Jin
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Maolin
authors.initials: M
authors.lastname: Zhang
authors.forename: Lianyi
authors.initials: L
authors.lastname: Xu
authors.forename: Qianju
authors.initials: Q
authors.lastname: Wu
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Zhu
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Huang
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D048049:Extracellular Signal-Regulated MAP Kinases