title: Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells.
abstract: A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.
authors.affiliation: First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takada
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Naoya
authors.initials: N
authors.lastname: Ichioka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ueda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Taira
authors.forename: Susumu
authors.initials: S
authors.lastname: Baba
authors.forename: Tomomi
authors.initials: T
authors.lastname: Mizokami
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hisha
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Iida
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D015519:Bone Density; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism*; D017154:Stromal Cells / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000596:Amino Acids; D000954:Antigens, Surface; D016207:Cytokines; D012333:RNA, Messenger; C036020:deoxypyridinoline