scholarly journals Targeted Disruption of the Wnt Regulator Kremen Induces Limb Defects and High Bone Density

2008 ◽  
Vol 28 (15) ◽  
pp. 4875-4882 ◽  
Author(s):  
Kristina Ellwanger ◽  
Hiroaki Saito ◽  
Philippe Clément-Lacroix ◽  
Nicole Maltry ◽  
Joachim Niedermeyer ◽  
...  
Keyword(s):  
Bone Formation ◽  
Limb Development ◽  
Critical Role ◽  
Functional Interaction ◽  
Triple Mutant ◽  
Targeted Disruption ◽  
Normal Bone ◽  
Physiological Relevance ◽  
High Bone ◽  
High Bone Density

ABSTRACT Kremen1 and Kremen2 (Krm1 and Krm2) are transmembrane coreceptors for Dickkopf1 (Dkk1), an antagonist of Wnt/β-catenin signaling. The physiological relevance of Kremen proteins in mammals as Wnt modulators is unresolved. We generated and characterized Krm mutant mice and found that double mutants show enhanced Wnt signaling accompanied by ectopic postaxial forelimb digits and expanded apical ectodermal ridges. Triple mutant Krm1 −/ − Krm2 −/ − Dkk1 +/ − mice show enhanced growth of ectopic digits, indicating that Dkk1 and Krm genes genetically interact during limb development. Wnt/β-catenin signaling also plays a critical role in bone formation. Single Krm mutants show normal bone formation and bone mass, while double mutants show increased bone volume and bone formation parameters. Our study provides the first genetic evidence for a functional interaction of Kremen proteins with Dkk1 as negative regulators of Wnt/β-catenin signaling and reveals that Kremen proteins are not universally required for Dkk1 function.

scholarly journals Monosodium Glutamate-Sensitive Hypothalamic Neurons Contribute to the Control of Bone Mass

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3842-3847 ◽  
Author(s):  
Florent Elefteriou ◽  
Shu Takeda ◽  
Xiuyun Liu ◽  
Dawna Armstrong ◽  
Gerard Karsenty
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Monosodium Glutamate ◽  
Hypothalamic Neurons ◽  
High Bone Mass ◽  
Independent Manner ◽  
Normal Bone ◽  
High Bone ◽  
High Bone Mass Phenotype

Abstract Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

scholarly journals Age-Related Association of Calcitonin with Parameters of Anthropometry, Bone and Calcium Metabolism during Childhood

2020 ◽  
pp. 1-10
Author(s):  
Juliane Sonntag ◽  
Mandy Vogel ◽  
Mandy Geserick ◽  
Felix Eckelt ◽  
Antje Körner ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Growth ◽  
Venous Blood ◽  
Physiological Role ◽  
Blood Levels ◽  
Childhood And Adolescence ◽  
Procollagen Type ◽  
Child Study ◽  
Age Related ◽  
High Bone

<b><i>Introduction:</i></b> The thyroid parafollicular hormone calcitonin (CT) shows particularly high blood levels in early childhood, a period of high bone turnover, which decrease with increasing age. Data about the physiological role of CT during infancy, childhood, and adolescence are contradictory or lacking. <b><i>Objective:</i></b> We hypothesize that CT demonstrates age-related correlations with parameters of bone growth and turnover as well as with parameters of calcium homeostasis. <b><i>Methods:</i></b> 5,410 measurements of anthropometric data and venous blood samples were collected from 2,636 participants of the LIFE Child study, aged 2 months–18 years. Univariate correlations and multiple regression analysis were performed between serum CT and anthropometric indicators (height standard deviation scores [SDS] and BMI-SDS), markers of calcium (Ca) homeostasis (Ca, parathyroid hormone, 25-OH vitamin D, and phosphate [P]), bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin), and bone resorption (β-CrossLaps). <b><i>Results:</i></b> CT was significantly associated with Ca (β = 0.26, <i>p</i> &#x3c; 0.05) and P1NP/100 (β = 0.005, <i>p</i> &#x3c; 0.05) in children aged 2 months–1.1 years. These relations were independent of age and sex and could not be confirmed in children aged 1.1–8 years. Independent of age, sex, puberty, P, and height SDS CT showed a significant positive relation to Ca (β = 0.26; <i>p</i> &#x3c; 0.001) in children aged 8–18 years. <b><i>Conclusions:</i></b> Our findings suggest a unique association between CT and Ca in periods of rapid bone growth and point to a possible involvement of CT in promoting bone formation during the first year of life.

scholarly journals SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Masatoshi Fukuda ◽  
Tatsuya Yoshizawa ◽  
Md. Fazlul Karim ◽  
Shihab U. Sobuz ◽  
Wataru Korogi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Critical Role

scholarly journals Overlapping Phenotypes in Osteopetrosis and Pycnodysostosis in Asian-Indians

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Parminder Kaur ◽  
Inusha Panigrahi ◽  
Harleen Kaur ◽  
Thakurvir Singh ◽  
Chakshu Chaudhry
Keyword(s):  
Hearing Loss ◽  
Bone Density ◽  
Genetic Heterogeneity ◽  
Asian Indians ◽  
Autosomal Dominant ◽  
Clinical Presentation ◽  
Epigenetic Alterations ◽  
High Bone ◽  
High Bone Density ◽  
Autosomal Dominant Osteopetrosis

Osteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature, acroosteolysis, and dense bones. We, hereby, present here a family with autosomal dominant osteopetrosis and also children with recessive osteopetrosis and pycnodysostosis. The molecular confirmation was done in 3 cases. Genetic heterogeneity in clinical presentation is discussed here. Further studies will help in identifying epigenetic alterations and population-specific variants and also developing targeted therapies.

scholarly journals Hematopoietic Wnts Modulate Endochondral Ossification During Fracture Healing

2021 ◽  
Vol 12 ◽  
Author(s):  
Kenon Chua ◽  
Victor K. Lee ◽  
Cheri Chan ◽  
Andy Yew ◽  
Eric Yeo ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Knockout Mice ◽  
Bone Repair ◽  
Critical Role ◽  
Computer Assisted ◽  
Stress Tests ◽  
Fracture Callus ◽  
Normal Bone ◽  
Musculoskeletal Development ◽  
Bone Quantity

Wnt signaling plays a critical role in bone formation, homeostasis, and injury repair. Multiple cell types in bone have been proposed to produce the Wnts required for these processes. The specific role of Wnts produced from cells of hematopoietic origin has not been previously characterized. Here, we examined if hematopoietic Wnts play a role in physiological musculoskeletal development and in fracture healing. Wnt secretion from hematopoietic cells was blocked by genetic knockout of the essential Wnt modifying enzyme PORCN, achieved by crossing Vav-Cre transgenic mice with Porcnflox mice. Knockout mice were compared with their wild-type littermates for musculoskeletal development including bone quantity and quality at maturation. Fracture healing including callus quality and quantity was assessed in a diaphyseal fracture model using quantitative micro computer-assisted tomographic scans, histological analysis, as well as biomechanical torsional and 4-point bending stress tests. The hematopoietic Porcn knockout mice had normal musculoskeletal development, with normal bone quantity and quality on micro-CT scans of the vertebrae. They also had normal gross skeletal dimensions and normal bone strength. Hematopoietic Wnt depletion in the healing fracture resulted in fewer osteoclasts in the fracture callus, with a resultant delay in callus remodeling. All calluses eventually progressed to full maturation. Hematopoietic Wnts, while not essential, modulate osteoclast numbers during fracture healing. These osteoclasts participate in callus maturation and remodeling. This demonstrates the importance of diverse Wnt sources in bone repair.

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