Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats

2009 ◽  
Vol 10 (10) ◽  
pp. 1470-1477 ◽  
Author(s):  
Nancy E. Lane ◽  
J.M. Thompson ◽  
Gordon J. Strewler ◽  
J.H. Kinney
Keyword(s):  
Parathyroid Hormone ◽  
Trabecular Bone ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Human Parathyroid Hormone ◽  
Intermittent Treatment

scholarly journals Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy

2015 ◽  
Vol 291 (4) ◽  
pp. 1631-1642 ◽  
Author(s):  
Partha Sinha ◽  
Piia Aarnisalo ◽  
Rhiannon Chubb ◽  
Ingrid J. Poulton ◽  
Jun Guo ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Phospholipase C ◽  
Osteoblast Differentiation ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Male And Female ◽  
Osteoblast Lineage

Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-GsαOsxKO mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1–34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-GsαOsxKO mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-GsαOsxKO mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation.

scholarly journals Parathyroid Hormone-Related Peptide Is Required for Increased Trabecular Bone Volume in Parathyroid Hormone-Null Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3554-3562 ◽  
Author(s):  
Dengshun Miao ◽  
Jiarong Li ◽  
Yingben Xue ◽  
Hanyi Su ◽  
Andrew C. Karaplis ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Development ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Osteoprogenitor Cell ◽  
Skeletal Phenotype ◽  
Pharmacological Potential ◽  
Changing Role

Abstract We investigated the relative contributions of PTH and PTHrP to the skeletal phenotype of mice deficient in PTH (PTH−/−). PTH−/− mice and PTH−/− mice lacking one allele encoding PTHrP (PTH−/−PTHrP+/−) were compared. Both mutants displayed similar biochemical abnormalities of hypoparathyroidism, but skeletal PTHrP mRNA and protein were decreased in PTH−/−PTHrP+/ − mice. PTH−/− mice had increased trabecular bone volume with diminished bone turnover. PTHrP haploinsufficiency reduced trabecular bone of the PTH−/− mice to levels below those in wild-type animals by decreasing osteoprogenitor cell recruitment, enhancing osteoblast apoptosis, and diminishing bone formation. The results show that the increased trabecular bone volume in PTH-deficient mice is due to diminished PTH-induced osteoclastic bone resorption and persistent PTHrP-stimulated osteoblastic bone formation. They also illustrate the changing role of PTHrP during bone development, demonstrate its bone- forming function in the postnatal state, and support its pharmacological potential as an anabolic agent.

scholarly journals Trabecular bone volume and osteoprotegerin expression in uremic rats given high calcium

2010 ◽  
Vol 25 (11) ◽  
pp. 2311-2319 ◽  
Author(s):  
Pornpimol Rianthavorn ◽  
Robert B. Ettenger ◽  
Isidro B. Salusky ◽  
Beatriz D. Kuizon
Keyword(s):  
Trabecular Bone ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
High Calcium

scholarly journals Bone health in spacefaring rodents and primates: systematic review and meta-analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingyan Fu ◽  
Matthew Goldsmith ◽  
Sequoia D. Crooks ◽  
Sean F. Condon ◽  
Martin Morris ◽  
...  
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Health ◽  
Volume Fraction ◽  
Meta Analysis ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Bone Volume Fraction ◽  
Percentage Difference ◽  
Induced Changes

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.

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

Cells ◽  
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.

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

1984 ◽  
Vol 29 (3) ◽  
pp. 171-175 ◽  
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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