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.

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.

Trabecular bone remodeling after seven days of weightlessness exposure (BIOCOSMOS 1667)

1988 ◽  
Vol 255 (2) ◽  
pp. R243-R247 ◽  
Author(s):  
L. Vico ◽  
D. Chappard ◽  
S. Palle ◽  
A. V. Bakulin ◽  
V. E. Novikov ◽  
...  
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Lumbar Vertebrae ◽  
Bone Volume ◽  
Male Rats ◽  
Long Bones ◽  
Trabecular Bone Volume ◽  
Detectable Change ◽  
Femoral Metaphysis ◽  
Trabecular Bone Mass

Seven male rats were exposed to 7 days of weightlessness in the Soviet mission COSMOS 1667 and compared with seven control rats by bone histomorphometric methods. In proximal tibial metaphysis, the trabecular bone volume was markedly reduced in flight animals. Trabeculae were decreased in number and thickness; this probably leads to alteration of bone mechanical properties. Formation activity (reflected by measurements of osteoid seams) was decreased at trabecular and endosteal levels. Resorption activity (estimated by count of osteoclast number and active resorption surfaces using a histoenzymologic method) remained unchanged. The imbalance between these cellular activities appears to be responsible for the loss of trabecular bone mass. In proximal femoral metaphysis, measurements were performed in an area located under the muscular insertions. The trabecular bone volume, despite a slight decrease in flight rats, was not significantly different from that of control rats. Furthermore, osteoclastic and osteoid parameters were unchanged. Differential responses between these two long bones need additional investigations. In thoracic and lumbar vertebrae no detectable change in bone mass and bone resorption parameters was found.

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 Disruption of the p53 Gene Results in Preserved Trabecular Bone Mass and Bone Formation After Mechanical Unloading

2002 ◽  
Vol 17 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Akinori Sakai ◽  
Takeshi Sakata ◽  
Shinya Tanaka ◽  
Ryuji Okazaki ◽  
Naoki Kunugita ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
P53 Gene ◽  
Mechanical Unloading ◽  
Trabecular Bone Mass

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.

scholarly journals Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 144-152 ◽  
Author(s):  
M. L. Bouxsein ◽  
M. J. Devlin ◽  
V. Glatt ◽  
H. Dhillon ◽  
D. D. Pierroz ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Weight ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Adrenergic Receptors ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Mineral Density ◽  
Adrenergic Signaling ◽  
Β Adrenergic Receptors

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..

Sign in / Sign up

Export Citation Format

Share Document