Tissue-Level Mechanisms Responsible for the Increase in Bone Formation and Bone Volume by Sclerostin Antibody

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.

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Trabecular Bone is Increased in a Rat Model of Polycystic Ovary Syndrome

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1284-5491 ◽

2020 ◽

Author(s):

Lady Katerine Serrano Mujica ◽

Werner Giehl Glanzner ◽

Amanda Luiza Prante ◽

Vitor Braga Rissi ◽

Gabrielle Rebeca Everling Correa ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Bone Formation ◽

Type I Collagen ◽

Polycystic Ovary ◽

Osteoclast Differentiation ◽

Bone Volume ◽

Negative Regulator ◽

Type I ◽

Ovary Syndrome ◽

The Impact

AbstractPolycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

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Regulation of bone repletion in rats subjected to varying low-calcium stress

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.246.2.r190 ◽

1984 ◽

Vol 246 (2) ◽

pp. R190-R196 ◽

Cited By ~ 1

Author(s):

R. H. Drivdahl ◽

C. C. Liu ◽

D. J. Baylink

Keyword(s):

Bone Formation ◽

Formation Rate ◽

Bone Volume ◽

Strong Positive Correlation ◽

Sprague Dawley ◽

Bone Formation Rate ◽

Osteoblast Activity ◽

Calcium Stress ◽

Sprague Dawley Rats ◽

Very High

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

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Sclerostin antibody enhances bone formation in a rat model of distraction osteogenesis

Journal of Orthopaedic Research® ◽

10.1002/jor.23726 ◽

2018 ◽

Cited By ~ 2

Author(s):

Michelle M. McDonald ◽

Alyson Morse ◽

Oliver Birke ◽

Nicole Y. C. Yu ◽

Kathy Mikulec ◽

...

Keyword(s):

Bone Formation ◽

Distraction Osteogenesis ◽

Rat Model ◽

Sclerostin Antibody

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Prolyl Hydroxylase Domain-Containing Protein 3 Gene Expression in Chondrocytes Is Not Essential for Bone Development in Mice

Cells ◽

10.3390/cells10092200 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2200

Author(s):

Weirong Xing ◽

Sheila Pourteymoor ◽

Gustavo A. Gomez ◽

Yian Chen ◽

Subburaman Mohan

Keyword(s):

Gene Expression ◽

Bone Formation ◽

Bone Mass ◽

Trabecular Bone ◽

Bone Volume ◽

Endochondral Bone Formation ◽

Chondrocyte Differentiation ◽

Trabecular Bone Volume ◽

Endochondral Bone ◽

Trabecular Bone Mass

We previously showed that conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in long bone trabecular bone mass. Loss of Phd2 gene expression or inhibition of PHD2 activity by a specific inhibitor resulted in a several-fold compensatory increase in Phd3 expression in chondrocytes. To determine if expression of PHD3 plays a role in endochondral bone formation, we conditionally disrupted the Phd3 gene in chondrocytes by crossing Phd3 floxed (Phd3flox/flox) mice with Col2α1-Cre mice. Loss of Phd3 expression in the chondrocytes of Cre+; Phd3flox/flox conditional knockout (cKO) mice was confirmed by real time PCR. At 16 weeks of age, neither body weight nor body length was significantly different in the Phd3 cKO mice compared to Cre−; Phd3flox/flox wild-type (WT) mice. Areal BMD measurements of total body as well as femur, tibia, and lumbar skeletal sites were not significantly different between the cKO and WT mice at 16 weeks of age. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype difference was found for any of the trabecular bone measurements of either the femur or the tibia. Trabecular bone volume of distal femur epiphysis was not different between cKO and WT mice. Histology analyses revealed Phd3 cKO mice exhibited a comparable chondrocyte differentiation and proliferation, as evidenced by no changes in cartilage thickness and area in the cKO mice as compared to WT littermates. Consistent with the in vivo data, lentiviral shRNA-mediated knockdown of Phd3 expression in chondrocytes did not affect the expression of markers of chondrocyte differentiation (Col2, Col10, Acan, Sox9). Our study found that Phd2 but not Phd3 expressed in chondrocytes regulates endochondral bone formation, and the compensatory increase in Phd3 expression in the chondrocytes of Phd2 cKO mice is not the cause for increased trabecular bone mass in Phd2 cKO mice.

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Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice

Bone ◽

10.1016/j.bone.2021.116201 ◽

2021 ◽

pp. 116201

Author(s):

Kelsey A. Carpenter ◽

Reid Davison ◽

Shruti Shakthivel ◽

Kyle D. Anderson ◽

Frank C. Ko ◽

...

Keyword(s):

Bone Formation ◽

Bone Mass ◽

Phosphate Metabolism ◽

Sclerostin Antibody

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Bone Formation and Resorption as the Determinants of Trabecular Bone Volume in Normal and Osteoporotic Men

Scottish Medical Journal ◽

10.1177/003693308402900307 ◽

1984 ◽

Vol 29 (3) ◽

pp. 171-175 ◽

Cited By ~ 16

Author(s):

B. E. C. Nordin ◽

J. Aaron ◽

R. Speed ◽

R. M. Francis ◽

N. Makins

Keyword(s):

Bone Formation ◽

Trabecular Bone ◽

Inverse Function ◽

Positive Function ◽

Bone Volume ◽

Trabecular Bone Volume ◽

Age Related ◽

Osteoporosis In Men ◽

Spinal Osteoporosis ◽

The Mean

Trabecular bone volume, forming surface and percent surface resorption have been determined in iliac crest samples obtained post mortem from 43 young men and 49 elderly men and in biopsies obtained from 22 males with spinal osteoporosis. The mean bone volume was significantly lower in the old than in the young controls and significantly lower again in the osteoporotic cases. Forming surfaces were significantly lower in the old than the young controls but were not different as between old controls and cases of osteoporosis. Percent surface resorption was the same in young and old controls but significantly increased in the osteoporotics. Multiple regression analysis showed that trabecular bone volume was a significant positive function of forming surface and a significant inverse function of fractional surface resorption. Age-related (simple) osteoporosis in men appears to be due to reduced bone formation whereas pathological (accelerated) osteoporosis is due to increased bone resorption.

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