scholarly journals The Deleterious Effects of Impaired Fibrinolysis on Skeletal Development Are Dependent on Fibrin(ogen), but Independent of Interlukin-6

2021 ◽  
Vol 8 ◽  
Author(s):  
Heather A. Cole ◽  
Stephanie N. Moore-Lotridge ◽  
Gregory D. Hawley ◽  
Richard Jacobson ◽  
Masato Yuasa ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Skeletal Growth ◽  
Vascular Changes ◽  
Fibrin Deposition ◽  
Growth Disturbances ◽  
Inflammatory Conditions ◽  
Skeletal Changes ◽  
Skeletal Phenotype ◽  
Intimate Link ◽  
Obesity And Cancer

Chronic diseases in growing children, such as autoimmune disorders, obesity, and cancer, are hallmarked by musculoskeletal growth disturbances and osteoporosis. Many of the skeletal changes in these children are thought to be secondary to chronic inflammation. Recent studies have likewise suggested that changes in coagulation and fibrinolysis may contribute to musculoskeletal growth disturbances. In prior work, we demonstrated that mice deficient in plasminogen, the principal protease of degrading and clearing fibrin matrices, suffer from inflammation-driven systemic osteoporosis and that elimination of fibrinogen resulted in normalization of IL-6 levels and complete rescue of the skeletal phenotype. Given the intimate link between coagulation, fibrinolysis, and inflammation, here we determined if persistent fibrin deposition, elevated IL-6, or both contribute to early skeletal aging and physeal disruption in chronic inflammatory conditions. Skeletal growth as well as bone quality, physeal development, and vascularity were analyzed in C57BL6/J mice with plasminogen deficiency with and without deficiencies of either fibrinogen or IL-6. Elimination of fibrinogen, but not IL-6, rescued the skeletal phenotype and growth disturbances in this model of chronic disease. Furthermore, the skeletal phenotypes directly correlated with both systemic and local vascular changes in the skeletal environment. In conclusion, these results suggest that fibrinolysis through plasmin is essential for skeletal growth and maintenance, and is multifactorial by limiting inflammation and preserving vasculature.

Exercise Can Reverse the Phenotype of Biglycan Deficient Mice

2003 ◽  
Author(s):  
Joseph M. Wallace ◽  
Rupak M. Rajachar ◽  
Xiao-Dong Chen ◽  
Songtao Shi ◽  
Matthew R. Allen ◽  
...  
Keyword(s):  
Skeletal Development ◽  
Skeletal Growth ◽  
Treadmill Running ◽  
Wild Type ◽  
Connective Tissues ◽  
Cross Sectional ◽  
Age Dependent ◽  
Skeletal Phenotype ◽  
Deficient Mice ◽  
Wild Type Control

Biglycan (Bgn) is a small leucine-rich proteoglycan (SLRP) that is enriched in bone and other skeletal connective tissues and is responsible, in part, for the regulation of postnatal skeletal growth (Bianco, 1990). Mice lacking Bgn display reduced skeletal development and a lower peak bone mass that leads to age-dependent osteopenia (Xu, 1998). We hypothesized that mechanical loading could reverse the skeletal phenotype of Bgn knockout mice. To test this hypothesis, we determined the effects of treadmill running on the geometric, mechanical and mineral properties of Bgn deficient mice bones. After sacrifice, femora and tibiae were tested in 4 point bending and cross-sectional geometric properties and bone mineral parameters were measured. Exercise was able to partially reverse the skeletal phenotype of the Bgn knockouts by increasing both the geometric and mechanical properties of the tibiae to values equal to or greater than those of wild type control mice.

Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth

1994 ◽  
Vol 267 (2) ◽  
pp. E278-E286 ◽  
Author(s):  
D. D. Bikle ◽  
J. Harris ◽  
B. P. Halloran ◽  
C. T. Roberts ◽  
D. Leroith ◽  
...  
Keyword(s):  
Growth Factors ◽  
Fetal Development ◽  
Skeletal Development ◽  
Skeletal Growth ◽  
Mrna Levels ◽  
Igf I ◽  
Bone Changes ◽  
Rat Bone ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I.

Correlation of Dental Maturity with Skeletal Maturity from Radiographic Assessment

2012 ◽  
Vol 36 (3) ◽  
pp. 309-314 ◽  
Author(s):  
John M. Morris ◽  
Jae Hyun Park
Keyword(s):  
Skeletal Maturity ◽  
Skeletal Development ◽  
Skeletal Growth ◽  
Dental Development ◽  
Radiographic Assessment ◽  
Additional Radiation ◽  
Dental Radiographs ◽  
Radiographic Interpretation ◽  
The Relationship ◽  
Dental Maturity

There have been many attempts to correlate dental development with skeletal growth. The relationship is generally considered to be moderate at best. However, there is evidence that hand-wrist radiographic interpretation of remaining growth can be augmented by taking into account the developing dentition. In addition, the practicality of evaluating routine dental radiographs and avoiding additional radiation is advantageous. To this point, no system has been described to match apical development by Demirjian’s stages and compare it to skeletal development and remaining growth. This study reviewed articles pertinent to the relationship between developing teeth and skeletal maturity and remaining growth, and a system is proposed to give practitioners an additional assessment for growth and development.

Skeletal Changes during the Treatment of Class II/I Malocclusions

1983 ◽  
Vol 10 (3) ◽  
pp. 147-153 ◽  
Author(s):  
A. M. Cohen
Keyword(s):  
Class Ii ◽  
Skeletal Growth ◽  
Skeletal Changes ◽  
Skeletal Pattern ◽  
Removable Appliance

Three groups of Class II/I patients were compared where treatment was carried out using Begg, Andresen and removable appliance techniques. Skeletal growth, as assessed by the dimensions S-Me, N-Me, ALFH and Me-Ar did not show any difference between the groups. All three groups showed an apparent improvement in skeletal pattern during treatment.

scholarly journals Animal models to explore the effects of glucocorticoids on skeletal growth and structure

2018 ◽  
Vol 236 (1) ◽  
pp. R69-R91 ◽  
Author(s):  
Claire L Wood ◽  
Ondrej Soucek ◽  
Sze C Wong ◽  
Farasat Zaman ◽  
Colin Farquharson ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Retardation ◽  
Chronic Conditions ◽  
Skeletal Development ◽  
Experimental Studies ◽  
Skeletal Growth ◽  
Clinical Model ◽  
Pros And Cons ◽  
Induced Changes

Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An in vivo model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a well-characterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.

scholarly journals The skeletal phenotypes of TRα and TRβ mutant mice

2008 ◽  
Vol 42 (4) ◽  
pp. 269-282 ◽  
Author(s):  
J H Duncan Bassett ◽  
Graham R Williams
Keyword(s):  
Molecular Mechanisms ◽  
Skeletal Development ◽  
Mutant Mice ◽  
Treatment Of Osteoporosis ◽  
Regulatory Pathways ◽  
Osteoclastic Resorption ◽  
Growth Factor Signalling ◽  
Skeletal Phenotype ◽  
Parathyroid Hormone Related Peptide ◽  
Adult Bone

Analysis of mice harbouring deletions or mutations of T3 receptor α (TRα) and β (TRβ) have clarified the complex relationship between central and peripheral thyroid status and emphasised the essential but contrasting roles of T3 in skeletal development and adult bone. These studies indicate that TRα1 is the predominant TR expressed in bone and that T3 exerts anabolic actions during growth but catabolic actions in the adult skeleton. Examination of key skeletal regulatory pathways in TR mutant mice has identified GH, IGF-1 and fibroblast growth factor signalling and the Indian hedgehog/parathyroid hormone-related peptide feedback loop as major targets of T3 action in chondrocytes and osteoblasts. Nevertheless, although increased osteoclastic resorption is a major feature of thyrotoxic bone loss and altered osteoclast activity is central to the skeletal phenotype of TR mutant mice, it remains unclear whether T3 has direct actions in osteoclasts. Detailed future analysis of the molecular mechanisms of T3 action in bone will enhance our understanding of this emerging field and has the potential to identify novel strategies for the prevention and treatment of osteoporosis.

Symptomatic osteochondroma of the spine in elderly patients

2009 ◽  
Vol 11 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Mitsuru Yagi ◽  
Ken Ninomiya ◽  
Michiya Kihara ◽  
Yukio Horiuchi
Keyword(s):  
Psoriatic Arthritis ◽  
Elderly Patients ◽  
Bone Turnover ◽  
Facet Joint ◽  
Clinical Symptoms ◽  
Skeletal Development ◽  
Relevant Literature ◽  
Clinical History ◽  
Skeletal Growth ◽  
First Case

Whereas osteochondroma is a common benign bone tumor in adolescence, it is rarely observed in elderly patients. It is unknown why osteochondromas, which usually develop during skeletal growth, rarely develop in elderly patients. The authors report 3 cases of symptomatic spinal osteochondroma in elderly patients and discuss the possible reasons for the onset of the enlargement of osteochondromas in elderly patients. Clinical history, radiographs, MR images, and CT myelography studies were obtained in each patient and are described. A review of the relevant literature is also presented. In the first case, the cervical osteochondroma caused spinal canal compression and occipital nerve irritation. It was totally excised, which successfully relieved the pain and allowed the patient to return to normal neurological function. In the second case, total removal of the tumor was effective in alleviating clinical symptoms. In the last case, ablation of the articular facet joint partially relieved the patient's lower-back pain. In the first 2 cases, the patients suffered from psoriasis and associated psoriatic arthritis and in the last case, the patient suffered from HIV-associated psoriatic arthritis. The psoriatic arthritis was characterized as asymmetric chronic multiple-joint arthritis and was HLA B27 positive. The pathology of psoriatic arthritis was the accelerating bone turnover and ankylosis. Symptomatic osteochondroma of the spine in elderly patients is extremely rare since it typically develops during skeletal growth. In this report, the authors show that pathological accelerating bone turnover such as psoriatic arthritis may be a possible mechanism for the onset of the enlargement of osteochondromas in elderly patients. The age of the patients in this report suggests that growth of the osteochondroma continues after skeletal development.

scholarly journals Haploinsufficiency of osterix in chondrocytes impairs skeletal growth in mice

2013 ◽  
Vol 45 (19) ◽  
pp. 917-923 ◽  
Author(s):  
Shaohong Cheng ◽  
Weirong Xing ◽  
Xin Zhou ◽  
Subburaman Mohan
Keyword(s):  
Bone Growth ◽  
Skeletal Growth ◽  
Endochondral Bone Formation ◽  
Volumetric Bone Mineral Density ◽  
Mineral Density ◽  
Endochondral Bone ◽  
Alizarin Red ◽  
Adult Mice ◽  
Elevated Expression ◽  
Skeletal Phenotype

Osterix ( Osx) is essential for both intramembranous or endochondral bone formation. Osteoblast-specific ablation of Osx using Col1α1-Cre resulted in osteopenia, because of impaired osteoblast differentiation in adult mice. Since Osx is also known to be expressed in chondrocytes, we evaluated the role of Osx expressed in chondrocytes by examining the skeletal phenotype of mice with conditional disruption of Osx in Col2α1-expressing chondrocytes. Surprisingly, Cre-positive mice that were homozygous for Osx floxed alleles died after birth. Alcian blue and alizarin red staining revealed that the lengths of skeleton, femur, and vertebrae were reduced by 21, 26, and 14% ( P < 0.01), respectively, in the knockout (KO) compared with wild-type mice. To determine if haploid insufficiency of Osx in chondrocytes influenced postnatal skeletal growth, we compared skeletal phenotype of floxed heterozygous mice that were Cre-positive or Cre-negative. Body length was reduced by 8% ( P < 0.001), and areal BMD of total body, femur, and tibia was reduced by 5, 7, and 8% ( P < 0.05), respectively, in mice with conditional disruption of one allele of Osx in chondrocytes. Micro-CT showed reduced cortical volumetric bone mineral density and trabecular bone volume to total volume in the femurs of Osxflox/+; col2α1-Cre mice. Histological analysis revealed that the impairment of longitudinal growth was associated with disrupted growth plates in the Osxflox/+; col2α1-Cre mice. Primary chondrocytes isolated from KO embryos showed reduced expression of chondral ossification markers but elevated expression of chondrogenesis markers. Our findings indicate that Osx expressed in chondrocytes regulates bone growth in part by regulating chondrocyte hypertrophy.

scholarly journals Skeletal development in the foetal and neonatal marmoset (Callithrix jacchus)

1976 ◽  
Vol 10 (3) ◽  
pp. 317-333 ◽  
Author(s):  
I. R. Phillips
Keyword(s):  
Skeletal Development ◽  
In Utero ◽  
Callithrix Jacchus ◽  
Primate Species ◽  
Developmental Status ◽  
Qualitative And Quantitative ◽  
Prenatal Growth ◽  
Skeletal Changes ◽  
Quantitative Measurements

Qualitative and quantitative measurements of skeletal development were performed on foetal marmosets in utero and on fixed specimens of both foetuses and neonates. The sequence of skeletal changes may be used to assess developmental status and the prenatal growth of the marmoset is compared with that of other primate species.

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