Bone Mass Distribution of the Distal Tibia in Normal, Osteopenic, and Osteoporotic Conditions: An Ex Vivo Assessment Using HR-pQCT, DXA, and Computational Modelling

Objective: Icariin (ICA), an extract from epimedium, has been reported to be effective in promoting bone formation. The objective of the study is to search for the molecular targets of ICA in bone mesenchymal stem cells (bMSCs) from the mice with ovariectomy (OVX)-induced osteoporosis. Methods: Six-month-old Imprinting Control Region (ICR) mice that underwent OVX were treated with ICA. After three months, bone mass was evaluated by microcomputed tomography, morphometry and immunohistological detection. bMSCs were isolated from the femur and tibia to observe the self-renewal and differentiation capacities using colony-forming unit fibroblastic (CFU-F), colony-forming unit adipocyte (CFU-Adipo) and alkaline phosphatase (ALP) staining. In addition, microarray of bMSCs ex vivo was measured two weeks after ICA treatment and analyzed by heatmap and pathway analysis. The signaling pathway was further explored by western blot assay and inhibitors of p38 and ERK: SB203508 and PD98059. Results: [Formula: see text]CT displayed a decrease in bone mass for three months after OVX. ICA treatment increased the trabecular thickness (Tb.Th), osteoblast number while decreased osteoclast number, elevating osteocalcin (OC) protein levels in vivo and facilitating the self-renewal and osteoblastic differentiation of bMSCs ex vivo. Microarray data indicated ICA rescued several gene expressions that were dysregulated by OVX. Pathway analysis revealed that the core genes acted by ICA were highly involved in MAPK signaling pathway. Further study demonstrated ICA suppressed ERK while stimulated p38 phosphorylation to promote osteoblastic differentiation in vitro. Conclusion: ICA promotes osteoblastic differentiation of bMSCs in OVX mice. MAPK signaling pathway might be involved in the process.

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GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice

Communications Biology ◽

10.1038/s42003-020-01564-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Jin-Ran Chen ◽

Haijun Zhao ◽

Umesh D. Wankhade ◽

Sree V. Chintapalli ◽

Can Li ◽

...

Keyword(s):

Bone Marrow ◽

Bone Resorption ◽

Bone Mass ◽

Hippuric Acid ◽

Ex Vivo ◽

Marrow Cell ◽

Osteoclast Differentiation ◽

Bone Homeostasis ◽

Wild Type ◽

Osteoclast Precursors

AbstractThe G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A−/−) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A−/− mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A−/− mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A−/− mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A−/− mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

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Influence of a School-based Physical Activity Intervention on Cortical Bone Mass Distribution: A 7-year Intervention Study

Calcified Tissue International ◽

10.1007/s00223-016-0174-y ◽

2016 ◽

Vol 99 (5) ◽

pp. 443-453 ◽

Cited By ~ 8

Author(s):

Jesper Fritz ◽

Rachel L. Duckham ◽

Timo Rantalainen ◽

Björn E. Rosengren ◽

Magnus K. Karlsson ◽

...

Keyword(s):

Physical Activity ◽

Bone Mass ◽

Cortical Bone ◽

Mass Distribution ◽

Intervention Study ◽

Physical Activity Intervention ◽

School Based ◽

Cortical Bone Mass

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Pelvis width associated with bone mass distribution at the proximal femur in children 10–11 years old

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-013-0478-1 ◽

2013 ◽

Vol 32 (2) ◽

pp. 174-183 ◽

Cited By ~ 4

Author(s):

Graça Cardadeiro ◽

Fátima Baptista ◽

Kathleen F. Janz ◽

Luís A. Rodrigues ◽

Luís B. Sardinha

Keyword(s):

Bone Mass ◽

Mass Distribution ◽

Proximal Femur

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Lifetime loading enhances cortical bone geometry and bone mass distribution in older men

Bone ◽

10.1016/j.bone.2009.01.218 ◽

2009 ◽

Vol 44 ◽

pp. S99-S100

Author(s):

C.A. Bailey ◽

S. Kukuljan ◽

R.M. Daly

Keyword(s):

Bone Mass ◽

Cortical Bone ◽

Mass Distribution ◽

Bone Geometry ◽

Older Men ◽

Cortical Bone Geometry

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The three-dimensional bone mass distribution of the posterior pelvic ring and its key role in transsacral screw placement

Scientific Reports ◽

10.1038/s41598-020-61954-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Darius M. Thiesen ◽

Dimitris Ntalos ◽

Josephine Berger-Groch ◽

Andreas Petersik ◽

Bernhard Hofstätter ◽

...

Keyword(s):

Bone Mass ◽

Mass Distribution ◽

Pelvic Ring ◽

Three Dimensional ◽

Screw Placement ◽

Posterior Pelvic Ring

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The Effect of Fructooligosaccharides with Various Degrees of Polymerization on Calcium Bioavailability in the Growing Rat

Experimental Biology and Medicine ◽

10.1177/153537020322800606 ◽

2003 ◽

Vol 228 (6) ◽

pp. 683-688 ◽

Cited By ~ 63

Author(s):

Marlena C. Kruger ◽

Katherine E. Brown ◽

Gabrielle Collett ◽

Lee Layton ◽

Linda M. Schollum

Keyword(s):

Bone Mass ◽

Bone Mineral ◽

Peak Bone Mass ◽

Calcium Absorption ◽

Bone Fractures ◽

Ex Vivo ◽

Later Life ◽

Male Rat ◽

Mineral Density ◽

Calcium Bioavailability

Maximizing peak bone mass during adolescence may be the key to postponing and perhaps preventing bone fractures due to osteoporosis in later life. One mechanism to maximize peak bone mass is to maximize calcium absorption, and it has been suggested that inulin and oligofructose might be one of the ways of doing so. In this study, fructooligosaccharides with various degrees of polymerization have been compared in terms of impact on calcium absorption, bone density, and excretion of collagen cross-links in the young adult male rat. The various oligosaccharides were oligofructose (DP2-8), inulin (DP>23), and a mixture of 92% inulin and 8% short-chain oligofructose (DP2-8). Measuring ex vivo bone mineral density (BMD) and bone mineral content (BMC) showed that BMD was significantly higher in the group fed inulin (DP>23) in both femurs, whereas BMC was significantly higher in the spine. The excretion of fragments of Type 1 collagen decreased in all groups over the 4 weeks of feeding, but the decrease was most significant in the group fed inulin (DP>23). Several hypotheses have been offered to explain the effect of the fructooligosaccharides on calcium absorption and retention. These include the production of organic acids that would acidify the luminal contents and enhance solubility and hence absorption, or possibly a mechanism via calbindinD9k. This study is unique in that it compares the different fructooligosaccharides in the same model, and it clearly shows that the various fructans do not have the same effect. In our model, inulin (DP>23) had the most significant effect on calcium bioavailability.

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Computational Modelling of Nephron Progenitor Cell Movement and Aggregation During Kidney Organogenesis

10.21203/rs.2.22766/v1 ◽

2020 ◽

Author(s):

Pauli Tikka ◽

Moritz Mercker ◽

Ilya Skovorodkin ◽

Ulla Saarela ◽

Seppo Vainio ◽

...

Keyword(s):

Cell Adhesion ◽

Potts Model ◽

Ex Vivo ◽

Computational Modelling ◽

Cell Movement ◽

Model Parameters ◽

Cellular Potts Model ◽

Kidney Organogenesis ◽

Nephron Progenitor ◽

Cell Cell

Abstract During early kidney organogenesis, nephron progenitor (NP) cells move from the tip to the corner region of the ureteric bud (UB) branches in order to form the pretubular aggregate, the early structure giving rise to nephron formation. Chemotaxis and cell-cell adhesion differences are believed to drive cell patterning during this critical period of organogenesis, but the spatiotemporal organization of this process is incompletely understood. We applied a Cellular Potts model to explore to how these processes contribute to directed cell movement and aggregation. Model parameters were estimated based on fitting to experimental data obtained in ex vivo kidney explant and dissociation-reaggregation organoid culture studies. Our simulations indicated that optimal enrichment and aggregation of NP cells in the UB corner niche requires chemoattractant secretion from both the UB epithelial cells and the NP cells themselves, as well as differences in cell-cell adhesion energies. Furthermore, NP cells were observed, both experimentally and by modelling, to move at higher speed in the UB corner as compared to the tip region where they originated. The existence of different cell speed domains along the UB was confirmed using self-organizing map analysis. In summary, we demonstrated the suitability of a Cellular Potts Model approach to simulate cell movement and patterning during early nephrogenesis. Further refinement of the model should allow us to recapitulate the effects of developmental changes of cell phenotypes and molecular crosstalk during organ development.

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