title: Expression and Role of Sonic Hedgehog in the Process of Fracture Healing with Aging.
abstract: Aging is one of the risk factors for delayed fracture healing. Sonic hedgehog (SHH) protein, an inducer of embryonic development, has been demonstrated to be activated in osteoblasts at the dynamic remodeling site of a bone fracture. Herein, we compared and examined the distribution patterns of SHH and the functional effect of SHH signaling on osteogenesis and osteoclastogenesis between young (5-week-old) and aged (60-week-old) mice during fracture healing. We found that SHH was expressed in bone marrow cells from the fractured site of the rib of young mice on day 5, but was barely detectable in the corresponding cells from the rib of aged mice. SHH was also detected in osteoblasts and bone marrow cells at the callus remodeling stage on days 14 and 28 in both young and aged mice. The number of alkaline phosphatase (ALP)-positive osteoblasts was significantly higher in young mice on days 5 and 14, whereas the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was significantly higher in aged mice. SHH stimulated significantly more osteoblast formation in the young compared to old mice. SHH stimulated the osteoclast formation directly in the aged mice and suppressed the formation indirectly through osteoprotegerin expression in the young mice. Results indicate that an aged-related delay of fracture healing may contribute to the unbalanced bone formation and resorption, regulated by hedgehog signaling.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan shimotsu@md.okayama-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Naito
authors.initials: N
authors.lastname: Kurio
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Okui
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Obata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Masui
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Department of Oromaxillofacial-Head and Neck Surgery, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Pai
authors.initials: P
authors.lastname: Pang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuu
authors.initials: Y
authors.lastname: Horikiri
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
mesh_terms: D000367:Age Factors; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D017102:Fracture Healing / Q000502:physiology*; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Fracture; aging; osteoblast; osteoclast; sonic hedgehog