scholarly journals Wnt16 exerts pleiotropic effects on bone and lean mass in zebrafish

2021 ◽  
Author(s):  
Claire J Watson ◽  
Ernesto Morfin Montes de Oca ◽  
Imke A K Fiedler ◽  
Andrea R Cronrath ◽  
LuLu K Callies ◽  
...  
Keyword(s):  
Lean Mass ◽  
Genetic Variants ◽  
Single Cell Analysis ◽  
Muscle Growth ◽  
Major Effect ◽  
Pleiotropic Effects ◽  
Mineral Density ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Critical Function

Identifying the mechanisms by which genetic variants exert pleiotropic effects on muscle and bone is a promising strategy to reveal molecular pathways that stimulate coupled bone and muscle growth, and which can be targeted to treat osteoporosis and sarcopenia simultaneously. Previously, it has been shown that genetic variants at the CPED1-WNT16 locus have pleiotropic effects on bone mineral density (BMD) and lean tissue mass in humans. While it is known that WNT16 is required for normal bone mass, our current functional understanding of WNT16 cannot account for dual effects on bone and lean mass at this locus. Using single cell analysis, microCT imaging, and genetic approaches, we reveal that wnt16 exerts pleiotropic effects on bone and lean tissue in zebrafish. We show an early influence of wnt16 on axial bone and lean tissue during skeletogenesis, and provide evidence that wnt16+ cells are myogenic precursors during embryonic development. We also show that wnt16 is a gene of major effect at the CPED1-WNT16 locus. Our findings indicate a critical function for wnt16 in muscle and lean tissue development and support WNT16 as the principal gene driving pleiotropic effects on bone and lean mass at this locus.

Bone and Lean Tissue Changes Following Cranial Cruciate Ligament Transection and Stifle Stabilization

2006 ◽  
Vol 42 (2) ◽  
pp. 127-135 ◽  
Author(s):  
David A. Francis ◽  
Darryl L. Millis ◽  
Laurie L. Head
Keyword(s):  
Bone Mineral Content ◽  
Bone Mineral ◽  
Mineral Content ◽  
Cruciate Ligament ◽  
Distal Tibia ◽  
Significant Loss ◽  
Mineral Density ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Cranial Cruciate Ligament

Following cranial cruciate ligament transection and extracapsular stabilization, dual-energy X-ray absorptiometry was used to analyze bone mineral content and lean tissue mass in the surgical and nonsurgical legs (n=14) at 0, 2, 4, and 8 weeks, and to evaluate bone mineral content and bone mineral density (BMD) of the proximal, mid-, and distal tibia of both the surgical and nonsurgical legs (n=15) at 0, 5, and 10 weeks. There was significant loss of bone mineral content and lean tissue in the surgical leg compared to the nonsurgical leg. Significant loss in bone mineral content and BMD was detected in the tibia of the surgical leg and was most pronounced in the metaphyseal region.

Contribution of lean tissue mass to the urban-rural difference in bone mineral density

2005 ◽  
Vol 16 (12) ◽  
pp. 1761-1768 ◽  
Author(s):  
Chatlert Pongchaiyakul ◽  
Tuan V. Nguyen ◽  
Vongsvat Kosulwat ◽  
Nipa Rojroongwasinkul ◽  
Somsri Charoenkiatkul ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Mineral Density ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Lean Tissue Mass ◽  
Urban Rural

Effect of a soluble activin receptor type IIB on androgen-deprivation-induced effects on body composition

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5133-5133
Author(s):  
J. Lachey ◽  
A. Koncarevic ◽  
J. Ucran ◽  
R. S. Pearsall ◽  
M. L. Sherman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Composition ◽  
Side Effects ◽  
Fat Mass ◽  
Lean Mass ◽  
Receptor Type ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Lean Tissue Mass ◽  
Adipose Mass

5133 Background: Androgen deprivation therapy (ADT) is a well-established treatment for hormone sensitive prostate cancer, but is associated with adverse side effects including loss of bone and lean mass and increased adipose mass. Activin receptor type IIB (ActRIIB) signaling is necessary for the negative regulation of lean tissue mass and treatment with a non-signaling, decoy ActRIIB results in a robust increase in lean tissue mass. Methods: Similar to ADT patients, orchiectomized (ORX) mice lose bone and lean mass and gain fat mass. To determine the therapeutic potential of inhibiting ActRIIB signaling to reduce the negative effects associated with ADT, we treated sham-operated (SHAM) and orchiectomized (ORX) mice with RAP-031, a fusion protein comprised of a form of the extracellular domain of ActRIIB linked to a murine Fc. Mice received twice weekly injections for 10 weeks with either vehicle (VEH) or 10 mg/kg RAP-031 (RAP). NMR scanning was used to determine body composition and whole body DEXA scans were performed to determine bone mineral density (BMD). Results: ORX resulted in a 4.4% decrease in BMD, an 18% reduction in lean tissue and a 41.6% increase in adiposity compared to the VEH-SHAM cohort. Both RAP-031treated groups of mice had significantly increased BMD and lean tissue mass and decreased adipose mass compared to their respective VEH groups. However, BMD, lean tissue and adiposity were not significantly different between the VEH-SHAM and RAP-ORX groups. These data illustrate that RAP-031 treatment completely attenuates ORX-induced alterations in bone, lean and fat mass. Conclusions: These data support the hypothesis that treatment with a form of soluble ActRIIB can offset negative side effects of ADT and have significant therapeutic implications for the treatment of patients with prostate cancer. [Table: see text] [Table: see text]

scholarly journals Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng Peng ◽  
Feng Liu ◽  
Kuan-Jui Su ◽  
Xu Lin ◽  
Yu-Qian Song ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Lean Mass ◽  
Genetic Variants ◽  
Genetic Basis ◽  
Functional Enrichment ◽  
Genome Wide Association Studies ◽  
Mineral Density ◽  
Appendicular Lean Mass ◽  
Shared Genetic

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein–protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

Effects of Long-Term Tennis Playing on the Muscle-Bone Relationship in the Dominant and Nondominant Forearms

2005 ◽  
Vol 30 (1) ◽  
pp. 3-17 ◽  
Author(s):  
Gaële Ducher ◽  
Christelle Jaffré ◽  
Alexandre Arlettaz ◽  
Claude-Laurent Benhamou ◽  
Daniel Courteix
Keyword(s):  
Bone Mineral Content ◽  
Grip Strength ◽  
Bone Mineral ◽  
Mineral Content ◽  
Whole Body ◽  
Mineral Density ◽  
Lean Tissue ◽  
Tissue Mass ◽  
The Relationship

The relationship between muscle strength and bone mineral density illustrates the positive effect of mechanical loading on bone. But local and systemic factors may affect both muscle and bone tissues. This study investigated the effects of long-term tennis playing on the relationship between lean tissue mass and bone mineral content in the forearms, taking the body dimensions into account. Fifty-two tennis players (age 24.2 ± 5.8 yrs, 16.2 ± 6.1 yrs of practice) were recruited. Lean tissue mass (LTM), bone area, bone mineral content (BMC), and bone mineral density were measured at the forearms from a DXA whole-body scan. Grip strength was assessed with a dynamometer. A marked side-to-side difference (p <  0.0001) was found in favor of the dominant forearm in all parameters. Bone area and BMC correlated with grip strength on both sides (r = 0.81-0.84, p <  0.0001). The correlations were still significant after adjusting for whole-body BMC, body height, or forearm length. This result reinforced the putative role of the muscles in the mechanical loading on bones. In addition, forearm BMC adjusted to LTM or grip strength was higher on the dominant side, suggesting that tennis playing exerts a direct effect on bone. Key words: bone mineral content, muscle strength, unilateral loading, mechanical stress, absorptiometry

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