title: rhPDGF-BB promotes proliferation and osteogenic differentiation of bone marrow stromal cells from streptozotocin-induced diabetic rats through ERK pathway.
abstract: Management of nonunion fracture and massive segmental bone defects in diabetes remains a challenging clinical problem. Bone marrow stromal cells (BMSCs) are crucial for bone remodeling and hold promise for bone regeneration. However, we have showed previously that diabetes can affect the proliferation and osteogenic potential of BMSCs adversely and a strategy to attenuate the impaired functions of BMSCs is required. Platelet-derived growth factor-BB (PDGF-BB) plays an important role in bone formation. However, little information is available about its effect on diabetic BMSCs. In this study, BMSCs were isolated from streptozotocin-induced diabetic rats. After treatment with recombinant human PDGF-BB (rhPDGF-BB), diabetic BMSCs demonstrated enhanced cell proliferation and osteogenic differentiation based on increased expressions of osteogenic genes (Runx2, alkaline phosphatase, and osteocalcin) and Runx2 protein, as well as upregulated alkaline phosphatase activity and mineralization. Furthermore, blocking extracellular signal regulated kinase (ERK) pathway by inhibitor PD98059 repressed the enhanced proliferation and osteogenic differentiation in diabetic BMSCs induced by rhPDGF-BB. Together, these results indicated that rhPDGF-BB stimulates proliferation and osteogenic differentiation partially through ERK pathway in diabetic BMSCs. Therefore, modulation of diabetic BMSCs could augment BMSCs function affected by diabetes and holds significance for future strategies to treat diabetic bone complications.
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China ; Department of Stomatology, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200011, China ; Shanghai Stomatological Diseases Center, Shanghai 200001, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Songmei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Lunguo
authors.identifier: 0000-0001-6154-9652
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Lamichhane
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China ; Oral Bioengineering Laboratory/Regenerative Medicine Lab, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Fuqiang
authors.identifier: 0000-0003-2570-6248
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001854:Bone Marrow Cells / Q000187:drug effects; D001861:Bone Regeneration / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D005419:Flavonoids / Q000008:administration & dosage; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats
chemical_list: D005419:Flavonoids; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one