Mouse tail vertebrae adapt to cyclic mechanical loading by increasing bone formation rate and decreasing bone resorption rate as shown by time-lapsed in vivo imaging of dynamic bone morphometry

Bone ◽  
2011 ◽  
Vol 49 (6) ◽  
pp. 1340-1350 ◽  
Author(s):  
Floor M. Lambers ◽  
Friederike A. Schulte ◽  
Gisela Kuhn ◽  
Duncan J. Webster ◽  
Ralph Müller
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Mechanical Loading ◽  
In Vivo Imaging ◽  
Formation Rate ◽  
Bone Formation Rate ◽  
Bone Morphometry ◽  
Resorption Rate ◽  
Bone Resorption Rate

Ovariectomy increases bone formation rate as well as bone resorption rate in mouse tail vertebra

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S165
Author(s):  
F.M. Lambers⁎ ◽  
K. Koch ◽  
F. Schulte ◽  
G. Kuhn ◽  
R. Müller
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Formation Rate ◽  
Bone Formation Rate ◽  
Resorption Rate ◽  
Tail Vertebra ◽  
Bone Resorption Rate

IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice

2001 ◽  
Vol 281 (2) ◽  
pp. E283-E288 ◽  
Author(s):  
Dennis L. Andress
Keyword(s):  
Bone Formation ◽  
Binding Protein ◽  
Formation Rate ◽  
Bone Matrix ◽  
Secretory Protein ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Ovariectomized Mice ◽  
Osteoblast Activity

Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast secretory protein that becomes incorporated into the mineralized bone matrix. In osteoblast cultures, IGFBP-5 stimulates cell proliferation by an IGF-independent mechanism. To evaluate whether IGFBP-5 can stimulate osteoblast activity and enhance bone accretion in a mouse model of osteoblast insufficiency, daily subcutaneous injections of either intact [IGFBP-5 (intact)] or carboxy-truncated IGFBP-5 [IGFBP-5-(1–169)] were given to ovariectomized (OVX) mice for 8 wk. Femur and spine bone mineral density (BMD), measured every 2 wk, showed early and sustained increases in response to IGFBP-5. Bone histomorphometry of cancellous bone showed significant elevations in the bone formation rate in both the femur metaphysis [IGFBP-5- (1)] only) and spine compared with OVX controls. IGFBP-5 also stimulated osteoblast number in the femur IGFBP-5-(1–169) only) and spine. These data indicate that IGFBP-5 effectively enhances bone formation and bone accretion in OVX mice by stimulating osteoblast activity. The finding that IGFBP-5-(1–169) is bioactive in vivo indicates that the carboxy-terminal portion is not required for this bone anabolic effect.

Bone changes due to pregnancy and lactation: influence of vitamin D status

1986 ◽  
Vol 251 (4) ◽  
pp. E400-E406 ◽  
Author(s):  
P. J. Marie ◽  
L. Cancela ◽  
N. Le Boulch ◽  
L. Miravet
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Formation Rate ◽  
Vitamin D Status ◽  
Bone Formation Rate ◽  
Bone Calcium ◽  
Pregnancy And Lactation ◽  
Stimulation Of

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.

Rest-inserted loading rapidly amplifies the response of bone to small increases in strain and load cycles

2007 ◽  
Vol 102 (5) ◽  
pp. 1945-1952 ◽  
Author(s):  
Sundar Srinivasan ◽  
Brandon J. Ausk ◽  
Sandra L. Poliachik ◽  
Sarah E. Warner ◽  
Thomas S. Richardson ◽  
...  
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Formation Rate ◽  
Load Cycle ◽  
Rest Interval ◽  
Bone Formation Rate ◽  
Dynamic Histomorphometry ◽  
Cyclical Loading ◽  
Strain Magnitude ◽  
The Right

We hypothesized that a 10-s rest interval (at zero load) inserted between each load cycle would increase the osteogenic effects of mechanical loading near previously identified thresholds for strain magnitude and cycle numbers. We tested our hypothesis by subjecting the right tibiae of female C57BL/6J mice (16 wk, n = 70) to exogenous mechanical loading within a peri-threshold physiological range of strain magnitudes and load cycle numbers using a noninvasive murine tibia loading device. Bone responses to mechanical loading were determined via dynamic histomorphometry. More specifically, we contrasted bone formation induced by cyclic vs. rest-inserted loading (10-s rest at zero load inserted between each load cycle) by first varying peak strains (1,000, 1,250, or 1,600 με) at fixed cycle numbers (50 cycles/day, 3 days/wk for 3 wk) and then varying cycle numbers (10, 50, or 250 cycles/day) at a fixed strain magnitude (1,250 με). Within the range of strain magnitudes tested, the slope of periosteal bone formation rate (p.BFR/BS) with increasing strain magnitudes was significantly increased by rest-inserted compared with cyclical loading. Within the range of load cycles tested, the slope of p.BFR/BS with increasing load cycles of rest-inserted loading was also significantly increased by rest-inserted compared with cyclical loading. In sum, the data of this study indicate that inserting a 10-s rest interval between each load cycle amplifies bone's response to mechanical loading, even within a peri-threshold range of strain magnitudes and cycle numbers.

1,25(OH)2D3 acts as a bone-forming agent in the hormone-independent senescence-accelerated mouse (SAM-P/6)

2005 ◽  
Vol 288 (4) ◽  
pp. E723-E730 ◽  
Author(s):  
Gustavo Duque ◽  
Michael Macoritto ◽  
Natalie Dion ◽  
Louis-Georges Ste-Marie ◽  
Richard Kremer
Keyword(s):  
Bone Formation ◽  
Bone Turnover ◽  
Bone Marrow Cells ◽  
Formation Rate ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Senile Osteoporosis ◽  
Dihydroxyvitamin D ◽  
Bone Formation Markers

Recent studies suggest that vitamin D signaling regulates bone formation. However, the overall effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on bone turnover in vivo is still unclear. In this study, our aim was to examine the effect of 1,25(OH)2D3 on bone turnover in SAM-P/6, a hormone-independent mouse model of senile osteoporosis characterized by a decrease in bone formation. Male and female 4-mo-old SAM-P/6 mice were treated with 1,25(OH)2D3 (18 pmol/24 h) or vehicle for a period of 6 wk, and a group of age- and sex-matched nonosteoporotic animals was used as control. Bone mineral density (BMD) at the lumbar spine increased rapidly by >30 ± 5% ( P < 0.001) in 1,25(OH)2D3-treated SAM-P/6 animals, whereas BMD decreased significantly by 18 ± 2% ( P < 0.01) in vehicle-treated SAM-P/6 animals and remained stable in control animals during the same period. Static and dynamic bone histomorphometry indicated that 1,25(OH)2D3 significantly increased bone volume and other parameters of bone quality as well as subperiosteal bone formation rate compared with vehicle-treated SAM-P/6 mice. However, no effect on trabecular bone formation was observed. This was accompanied by a marked decrease in the number of osteoclasts and eroded surfaces. A significant increase in circulating bone formation markers and a decrease in bone resorption markers was also observed. Finally, bone marrow cells, obtained from 1,25(OH)2D3-treated animals and cultured in the absence of 1,25(OH)2D3, differentiated more intensely into osteoblasts compared with those derived from vehicle-treated mice cultured in the same conditions. Taken together, these findings demonstrate that 1,25(OH)2D3 acts simultaneously on bone formation and resorption to prevent the development of senile osteoporosis.

The anabolic effect of 17β-oestradiol on the trabecular bone of adult rats is suppressed by indomethacin

1992 ◽  
Vol 133 (2) ◽  
pp. 189-195 ◽  
Author(s):  
J. W. M. Chow ◽  
J. M. Lean ◽  
T. Abe ◽  
T. J. Chambers
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Growth ◽  
Formation Rate ◽  
Bone Volume ◽  
Female Rats ◽  
Mineral Apposition Rate ◽  
Adult Rats ◽  
Bone Formation Rate

ABSTRACT We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17β-oestradiol (OE2)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE2 suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts. Journal of Endocrinology (1992) 133, 189–195

Effect of Minocycline on Osteoporosis

1998 ◽  
Vol 12 (1) ◽  
pp. 71-75 ◽  
Author(s):  
S. Williams ◽  
A. Wakisaka ◽  
Q.Q. Zeng ◽  
J. Barnes ◽  
S. Seyedin ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Formation Rate ◽  
Inhibitory Effect ◽  
Mineral Apposition Rate ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Trabecular Thickness ◽  
Trabecular Bone Area

The effect of oral minocycline on osteopenia in ovariectomized (OVX) old rats was examined in this study. Rats were divided into 4 groups: sham-operated, OVX followed by treatment with vehicle, minocycline, or 17β-estradiol. The treatment was initiated one day after OVX and proceeded for 8 wks. OVX reduced bone mineral density (BMD) in the whole femur and in the femoral regions that are enriched in trabecular bone. Treatment with minocycline or estrogen prevented a decrease in BMD. Femoral trabecular bone area, trabecular number, and trabecular thickness were reduced, and trabecular separation was increased by OVX. Treatment with minocycline or estrogen abolished the detrimental effects induced by OVX. OVX also reduced indices that reflect the interconnectivity of trabecular bone, and the loss of trabecular connectivity was prevented by treatment with minocycline or estrogen. Based on the levels of urinary pyridinoline, we showed that the effect of estrogen, but not minocycline, was primarily through its inhibitory effect on bone resorption. Analysis of bone turnover activity suggests that OVX increased parameters associated with bone resorption (eroded surface) and formation (osteoid surface, mineralizing surface, mineral apposition rate, and bone formation rate). Treatment with minocycline reduced bone resorption modestly and stimulated bone formation substantially. In contrast, treatment with estrogen drastically reduced parameters associated with both bone resorption and formation. We have concluded that oral minocycline can effectively prevent the decrease in BMD and trabecular bone through its dual effects on bone resorption and formation.

scholarly journals Mechanical Loading Shows Anti-Myeloma Effects While Rescuing Bone Loss with Net Bone Formation in a Myeloma Bone Disease Murine Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3164-3164
Author(s):  
Fani Ziouti ◽  
Maximilian Rummler ◽  
Andreas Brandl ◽  
Andreas Beilhack ◽  
Maureen Lynch ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Mechanical Loading ◽  
Bone Disease ◽  
Whole Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mechanical Stimuli

Abstract Osteolytic bone disease (BD) is a hallmark of multiple myeloma (MM) with tumor cells in the bone marrow shifting the balance of the bone remodeling process towards massive bone resorption. As a result, patients develop devastating osteolytic lesions that lead to non-healing bone fractures and pain, affecting life quality and mortality rates. Bones have the capacity to adapt mass and structure to mechanical stimuli, as dramatically seen in young tennis athletes with muscle-bone asymmetries in the playing arm. We have previously shown that tibial mechanical loading rescued bone loss in our murine MOPC315.BM MM model with an advanced osteolytic phenotype. Here, we hypothesize that mechanical strain (1) modulates the bone microenvironment and (2) has antitumor activity in mice. (1) We determined bone formation and bone resorption parameters by time-lapsed microCT analysis to show how skeletal mechanical stimuli control MM bone disease (MMBD) progression over time. (2) To monitor tumor progression, we used non-invasive bioluminescence imaging (BLI) and enzyme-linked immunosorbent assay (ELISA) for detection of MOPC315.BM specific immunoglobulin A (IgA) levels. In our in vivo loading study, we injected MOPC315.BM cells intratibially (i.t.) in BALB/c mice to establish MMBD (n=17) and used PBS-injected (n=13) as well as noninjected mice (n=8) as controls. Eight (MM), seven (PBS) and 8 (noninjected) mice received compressive tibial loading for three weeks while nine (MM) and six (PBS) mice served as nonloaded controls. The bone remodeling response to mechanical loading was investigated by longitudinal in vivo microCT imaging performed every 5 days (at day 13, 18, 23, 28, and 33 after i.t. injection). MicroCT images from day 33 were geometrically registered onto images of day 13 and resampled into the same coordinate system using Amira and scripts written in Matlab for post-processing. Normalized newly mineralized and eroded bone volume (MV/BV, EV/BV), normalized formed and eroded bone surface area (MS/BS, ES/BS), mineralized thickness (MTh) and eroded depth (ED) were quantified. ANOVA was performed to examine the effect of loading and injection. Loading significantly increased the periosteal MV/BV, periosteal and endosteal MS/BS as well as decreased the periosteal EV/BV and periosteal and endocortical ES/BS. Endosteal MV/BV or EV/BV were not affected, which may be due to differences in the local strain environment at the two surfaces. In addition, mechanical stimuli did not influence ED, but led to diminished periosteal EV/BV and periosteal ES/BS suggesting fewer resorption sites in tibiae subjected to loading. Injection significantly affected periosteal and endosteal bone formation and resorption (Fig.1). Significant increases in cortical bone mass of loaded MM mice were accompanied by decreases in tumor load as evidenced by MOPC315.BM specific IgA levels (Fig. 2A). Interestingly, quantification of tibial and whole body bioluminescence signal intensities revealed controlled tumor growth in the loaded left tibia and a further delay of tumor cell dissemination throughout body of MM mice (Fig. 2B). Our data provide evidence that skeletal mechanical stimuli have anti-myeloma effects and rescue osteolytic bone loss in MMBD. The anabolic response to mechanical loads outweighs the anti-resorptive effect of MM cells, suggesting a combination of loading with bone resorption inhibitors in future therapeutic strategies. Disclosures No relevant conflicts of interest to declare.

scholarly journals CD13 is a Critical Regulator of Cell-cell Fusion in Osteoclastogenesis

2020 ◽  
Author(s):  
Mallika Ghosh ◽  
Ivo Kalajzic ◽  
Hector Leonardo Aguila ◽  
Linda H Shapiro
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Progenitor Cells ◽  
Cell Fusion ◽  
Formation Rate ◽  
Giant Cells ◽  
Bone Formation Rate ◽  
Cell Cell

AbstractIn vertebrates, bone formation is dynamically controlled by the activity of two specialized cell types: the bone-generating osteoblasts and bone-degrading osteoclasts. Osteoblasts produce the soluble receptor activator of NFκB ligand (RANKL) that binds to its receptor RANK on the surface of osteoclast precursor cells to promote osteoclastogenesis, a process that involves cell-cell fusion and assembly of molecular machinery to ultimately degrade the bone. CD13 is a transmembrane aminopeptidase that is highly expressed in cells of myeloid lineage has been shown to regulate dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. In the present study, we show that CD13-deficient mice display a normal distribution of osteoclast progenitor populations in the bone marrow, but present a low bone density phenotype. Further, the endosteal bone formation rate is similar between genotypes, indicating a defect in osteoclast-specific function in vivo. Loss of CD13 led to exaggerated in vitro osteoclastogenesis as indicated by significantly enhanced fusion of bone marrow-derived multinucleated osteoclasts in the presence of M-CSF and RANKL, resulting in abnormally large cells with remarkably high numbers of nuclei with a concomitant increase in bone resorption activity. Similarly, we also observed increased formation of multinucleated giant cells (MGC) in CD13KO bone marrow progenitor cells stimulated with IL-4 and IL-13, suggesting that CD13 may regulate cell-cell fusion events via a common pathway, independent of RANKL signaling. Mechanistically, while expression levels of the fusion-regulatory proteins dynamin and DC-STAMP are normally downregulated as fusion progresses in fusion-competent mononucleated progenitor cells, in the absence of CD13 they are uniformly sustained at high levels, even in mature multi-nucleated osteoclasts. Taken together, we conclude that CD13 may regulate cell-cell fusion by controlling expression and localization of key fusion proteins that are critical for both osteoclast and MGC fusion.

scholarly journals Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair

2019 ◽  
Vol 5 (8) ◽  
pp. eaax2476 ◽  
Author(s):  
S. Herberg ◽  
A. M. McDermott ◽  
P. N. Dang ◽  
D. S. Alt ◽  
R. Tang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor ◽  
Bone Development ◽  
Formation Rate ◽  
Natural Fracture ◽  
Bone Morphogenetic Protein 2 ◽  
Long Bone ◽  
Bone Formation Rate ◽  
Tgf Β1

Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor–β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-β1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-β1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-β1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.

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