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Trabecular Bone Mineral Density (trabecular + bone_mineral_density)
Selected AbstractsLocal ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in miceTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Xiao S. Zhang Abstract Background Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV-based retroviral vector to express human bone morphogenetic protein 4 (BMP4). Methods We assessed two approaches for administering transduced MSCs. ,-Galactosidase (,-Gal) transduced C57BL/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4- or ,-Gal-transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X-ray, peripheral quantitative computed tomography (pQCT), and histology. Results After tail-vein injection less than 20% of recipient mice contained ,-Gal-positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02,0.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4-transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. Conclusions The present findings support the feasibility of using ex vivo MSC-based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites. Copyright © 2004 John Wiley & Sons, Ltd. [source] Two Different Pathways for the Maintenance of Trabecular Bone in Adult Male Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2002Marie K. Lindberg Abstract Androgens may regulate the male skeleton either directly via activation of the androgen receptor (AR) or indirectly via aromatization of androgens into estrogen and, thereafter, via activation of estrogen receptors (ERs). There are two known estrogen receptors, ER-, and ER-,. The aim of this study was to investigate the relative roles of ER-,, ER-,, and AR in the maintenance of trabecular bone in male mice. Seven-month-old male mice, lacking ER-, (ERKO), ER-, (BERKO), or both receptors (DERKO), were orchidectomized (orx) and treated for 3 weeks with 0.7 ,g/mouse per day of 17,-estradiol or vehicle. No reduction in trabecular bone mineral density (BMD) was seen in ERKO, BERKO, or DERKO mice before orx, showing that neither ER-, nor ER-, is required for the maintenance of a normal trabecular BMD in male mice. After orx, there was a pronounced decrease in trabecular BMD, similar for all groups, resulting in equal levels of trabecular BMD in all genotypes. This reduction was reversed completely in wild-type (WT) and BERKO mice treated with estrogen, and no significant effect of estrogen was found in ERKO or DERKO mice. In summary, the trabecular bone is preserved both by a testicular factor, presumably testosterone acting via AR and by an estrogen-induced activation of ER-,. These results indicate that AR and ER-, are redundant in the maintenance of the trabecular bone in male mice. In contrast, ER-, is of no importance for the regulation of trabecular bone in male mice. [source] Tibolone Exerts Its Protective Effect on Trabecular Bone Loss Through the Estrogen ReceptorJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001A. G. H. Ederveen Abstract Tibolone (Org OD14) has estrogenic, progestogenic, and/or androgenic activity depending on the tissue. In postmenopausal women, tibolone prevents bone loss without stimulating the endometrium. Tibolone is effective in preventing trabecular bone loss from the peripheral and axial skeleton of young and old ovariectomized (OVX) rats by reducing bone turnover, that is, bone resorption, like estrogens. We evaluated the contribution of the various hormonal activities to tibolone's bone-conserving effect. Three-month-old OVX rats received tibolone (125 ,g/rat or 500 ,g/rat, twice daily), alone or combined with an antiestrogen, antiandrogen, or antiprogestogen, and the effects on trabecular bone mass and bone turnover were evaluated. Sham-operated and control OVX groups were treated with vehicle. The remaining OVX groups received oral doses of tibolone twice daily, alone or with twice daily (a) antiestrogen ICI 164.384, (b) antiandrogen flutamide, or (c) antiprogestogen Org 31710. For comparison, the effects of 17,-estradiol and testosterone were examined also. After 4 weeks, trabecular bone mineral density (BMD) in the distal femur, plasma osteocalcin, and urinary deoxypyridinoline/creatinine ratio (Dpyr/Cr) were measured. Tibolone or 17,-estradiol significantly blocked ovariectomy-induced loss of trabecular BMD and inhibited bone resorption and bone turnover as judged by reduced Dpyr/Cr ratio and osteocalcin, respectively. These effects of both compounds were counteracted by the antiestrogen. This suggests a major involvement of the estrogen receptor in the action of tibolone on bone metabolism. However, the antiandrogen and the antiprogestogen did not counteract the effects of tibolone, excluding a major role of the androgenic and progestogenic activities of tibolone in its action against trabecular bone loss. The results indicate that tibolone acts on bone almost entirely through activation of the estrogen receptor. [source] Female Estrogen Receptor ,,/, Mice Are Partially Protected Against Age-Related Trabecular Bone LossJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2001Sara H. Windahl Abstract Recently, it has been shown that inactivation of estrogen receptor , (ER-,) by gene targeting results in increased cortical bone formation in adolescent female mice. To study the possible involvement of ER-, in the regulation of the mature skeleton, we have extended the analyses to include 1-year-old ER-, knockout mice (ER-,,/,). Male ER-,,/, mice did not express any significant bone phenotypic alterations at this developmental stage. However, the increase in cortical bone parameters seen already in the adolescent female ER-,,/, mice was maintained in the older females. The aged female ER-,,/, mice further exhibited a significantly higher trabecular bone mineral density (BMD) as well as increased bone volume/total volume (BV/TV) compared with wild-type (wt) mice. This was caused by a less pronounced loss of trabecular bone during adulthood in female ER-,,/, mice. The growth plate width was unaltered in the female ER-,,/, mice. Judged by the expression of the osteoclast marker tartrate-resistant acid phosphatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chain reaction [RT-PCR]) as well as the serum levels of C-terminal type I collagen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast marker core-binding factor ,1 (Cbfa1) suggested an anabolic effect in bones of old female ER-,,/, mice. In addition, the mRNA expression of ER-, was augmented, indicating a role for ER-, in the development of this phenotype. Taken together, the results show that ER-, is involved in the regulation of trabecular bone during adulthood in female mice and suggest that ER-, acts in a repressive manner, possibly by counteracting the stimulatory action of ER-, on bone formation. [source] Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administrationAGING CELL, Issue 5 2010Robert L. Jilka Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. Parathyroid hormone produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26- when compared to 6 -month-old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae, and the toughness of both vertebrae and femora in old, but not young, mice. Parathyroid hormone also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species, p66Shc phosphorylation, and expression of the lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in bone of old mice. Parathyroid hormone also antagonized the effects of oxidative stress on p66Shc phosphorylation, Forkhead Box O transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N -acetyl cysteine or pegylated catalase reduced osteoblast progenitors and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation, it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. [source] Reduced cortical bone mass in mice with inactivation of interleukin-4 and interleukin-13JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2007Carl-Johan Silfverswärd Abstract The aim of the present study was to study the in vivo role of IL-4 and IL-13 on bone metabolism. The skeletal phenotypes of male and female IL-13,/, (n,=,7+7), IL-4,/,IL-13,/, (n,=,7+7), and WT (n,=,7+7) mice were compared. Analysis was made at 6 weeks of age (juvenile) by pQCT, and at 20 weeks of age (adult) by pQCT, biomechanical testing, and by S-IGF-1 and S-Osteocalcin measurements. The skeletal phenotype was affected only in adult male IL-4,/,IL-13,/, mice. These animals displayed a reduction in cortical bone mineral content (BMC) of both the tibia and the femur, as measured by mid-diaphyseal pQCT scans, compared with WT mice (tibia ,8.2%; femur ,8.5%; p,<,0.01). This reduction in cortical BMC was due to a decreased cross-sectional area as a result of a reduced cortical thickness. The mechanical strength of the cortical bone, tested by three-point-bending at the mid-diaphyseal region of the femurs, demonstrated a significant reduction of displacement at failure (,11.4%), maximal load at failure (,10.6%), and total energy until failure (,29.4%). S-IGF-1 and S-Osteocalcin levels as well as trabecular bone mineral density (tvBMD) were unaffected in adult male IL-4,/,IL-13,/, mice. IL-4,/,IL-13,/, male mice show adult onset reduction of cortical bone mass and strength, indicating that the two anti-inflammatory Th2 cytokines IL-4 and IL-13 are involved in the regulation of bone remodeling. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25: 725,731, 2007 [source] | ||||||||||