The Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time‐dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in ...perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (MSC) and human peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through MT2 melatonin receptors, MEK1/2, and MEK5. In layered but not transwell cocultures, melatonin increased OPG:RANKL ratios by inhibiting RANKL, suggesting that contact with osteoclasts during osteoblastogenesis inhibits RANKL secretion. Melatonin modulated expression of ERK1/2, ERK5, β1 integrin, GLUT4, and IRβ that was dependent upon the type of coculture; however, in both cultures, melatonin increased RUNX2 and decreased PPARγ expression, indicating a role for metabolic processes that control osteogenic vs adipogenic cell fates of MSCs. Furthermore, melatonin also has osteoblast‐inducing effects on human adipose‐derived MSCs. In vivo, one‐year nightly melatonin (15 mg/L) given to neu female mice in their drinking water increased pErk1/2, pErk5, Runx2, and Opg and Rankl levels in bone consistent with melatonin's already reported bone‐enhancing effects. Finally, analysis of daily logs from the MOPS demonstrated a significant improvement in mood and perhaps sleep quality in women receiving melatonin vs placebo. The osteoblast‐inducing, bone‐enhancing effects of melatonin and improvement in quality of life suggest that melatonin is a safe and effective bone loss therapy.
Head collisions in sport can result in catastrophic injuries to the cervical spine. Musculoskeletal modelling can help analyse the relationship between motion, external forces and internal loads that ...lead to injury. However, impact specific musculoskeletal models are lacking as current viscoelastic values used to describe cervical spine joint dynamics have been obtained from unrepresentative quasi-static or static experiments. The aim of this study was to develop and validate a cervical spine musculoskeletal model for use in axial impacts. Cervical spine specimens (C2-C6) were tested under measured sub-catastrophic loads and the resulting 3D motion of the vertebrae was measured. Specimen specific musculoskeletal models were then created and used to estimate the axial and shear viscoelastic (stiffness and damping) properties of the joints through an optimisation algorithm that minimised tracking errors between measured and simulated kinematics. A five-fold cross validation and a Monte Carlo sensitivity analysis were conducted to assess the performance of the newly estimated parameters. The impact-specific parameters were integrated in a population specific musculoskeletal model and used to assess cervical spine loads measured from Rugby union impacts compared to available models. Results of the optimisation showed a larger increase of axial joint stiffness compared to axial damping and shear viscoelastic parameters for all models. The sensitivity analysis revealed that lower values of axial stiffness and shear damping reduced the models performance considerably compared to other degrees of freedom. The impact-specific parameters integrated in the population specific model estimated more appropriate joint displacements for axial head impacts compared to available models and are therefore more suited for injury mechanism analysis.
Abstract
The Melatonin Osteoporosis Prevention Study (
MOPS
) demonstrated that nightly melatonin resulted in a time‐dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in ...perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (
MSC
) and human peripheral blood monocytes (
PBMC
s). Human
MSC
/
PBMC
cocultures exposed to melatonin in osteogenic (
OS
+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through
MT
2 melatonin receptors,
MEK
1/2, and
MEK
5. In layered but not transwell cocultures, melatonin increased
OPG
:
RANKL
ratios by inhibiting
RANKL
, suggesting that contact with osteoclasts during osteoblastogenesis inhibits
RANKL
secretion. Melatonin modulated expression of
ERK
1/2,
ERK
5, β1 integrin,
GLUT
4, and
IR
β that was dependent upon the type of coculture; however, in both cultures, melatonin increased
RUNX
2 and decreased
PPAR
γ expression, indicating a role for metabolic processes that control osteogenic vs adipogenic cell fates of
MSC
s. Furthermore, melatonin also has osteoblast‐inducing effects on human adipose‐derived
MSC
s. In vivo, one‐year nightly melatonin (15 mg/L) given to
neu
female mice in their drinking water increased
pE
rk1/2,
pE
rk5, Runx2, and Opg and Rankl levels in bone consistent with melatonin's already reported bone‐enhancing effects. Finally, analysis of daily logs from the
MOPS
demonstrated a significant improvement in mood and perhaps sleep quality in women receiving melatonin vs placebo. The osteoblast‐inducing, bone‐enhancing effects of melatonin and improvement in quality of life suggest that melatonin is a safe and effective bone loss therapy.
BACKGROUND: The aim of the present study was to evaluate temporal changes on oral health knowledge and attitudes among two populations of young Greek males (age 19-29 years) undergoing their military ...training. A secondary aim was to identify socioeconomic trends that may have influenced the above. METHODS: A total of 2,764 healthy subjects (1511 in 1985, and 1253 in 1996) answered a standardized questionnaire of oral health issues. Respondents were stratified in 3 groups, according to their educational status (ES); their responses were compared using the chi-square statistic. The evaluation of socioeconomic indicators utilized longitudinal data from the national Household Expenditures Survey. RESULTS: An overall improvement was noted in the majority of "Knowledge" and "Attitudes" variables in 1996, as compared to 1985. Education seems to play an important role in both knowledge and attitudes. These changes may also be partially attributed to a shift in consuming standards from the coverage of main needs to income disposal directed towards the achievement of better quality of life.
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