title: Anabolic bone formation via a site-specific bone-targeting delivery system by interfering with semaphorin 4D expression.
abstract: Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China, China; Department of Dental Implantology, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lingfei
authors.initials: L
authors.lastname: Wei
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miron
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000517:prevention & control; D002454:Cell Differentiation; D018920:Coculture Techniques; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D010024:Osteoporosis / Q000473:pathology; D011108:Polymers; D034741:RNA, Small Interfering / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D014162:Transfection
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D011108:Polymers; D034741:RNA, Small Interfering; D039961:Semaphorins
keywords: BONE REMODELING; BONE TARGETING; OSTEOPOROSIS; SEMAPHORIN