title: N-acetyl cysteine as an osteogenesis-enhancing molecule for bone regeneration.
abstract: Bone regeneration often requires cues from osteogenesis-inducing factors for successful outcome. N-acetyl cysteine (NAC), an anti-oxidant small molecule, possibly modulates osteoblastic differentiation. This study investigated the potential of NAC as an osteogenesis-enhancing molecule in vitro and in vivo. Various concentrations of NAC (0, 2.5, 5.0, and 10 mM) were added to rat bone marrow stromal cell or osteoblastic cell culture in media with or without dexamethasone. The results showed marked enhancement of alkaline phosphatase activity and mineralized matrix formation together with consistent upregulation of bone-related gene markers such as collagen I, osteopontin, and osteocalcin in the osteoblastic culture with addition of 2.5 or 5.0 mM NAC regardless of the presence of dexamethasone. Micro-CT-based analysis and histological observation revealed that addition of NAC to a collagenous sponge implanted in a critical size cortical bone defect (3.0 mm × 5.0 mm) in rat femur yielded acceleration and completion of defect closure, with thick, compact, and contiguous bone after 6 weeks of healing. In contrast, with sponge alone, only sparse and incomplete bone regeneration was observed during the matching healing period. These results indicate that NAC can function as an osteogenesis-enhancing molecule to accelerate bone regeneration by activating differentiation of osteogenic lineages.
authors.affiliation: The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA. masayamada@tdc.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsukimura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sugita
authors.forename: Wael
authors.initials: W
authors.lastname: Att
authors.forename: Norinaga
authors.initials: N
authors.lastname: Kojima
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Kubo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sakurai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005269:Femur / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D000111:Acetylcysteine