Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.

/pdf/rankl-rank-opg-pathway-a-mechanism-involved-in-exercise-3hignemgax.pdf

RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling.

Objective: To investigate the 10-year risk of dementia in subjects with mild cognitive impairment (MCI) ages 40 to 85 years. Methods: We selected subjects from a memory clinic if they met one of the following definitions of MCI: cognitive complaints (n = 181), aging-associated cognitive decline (AACD) (n = 163), mild functional impairment (n = 86), or amnestic MCI (n = 64). Subjects were reassessed after 2, 5, and 10 years. The risk of dementia was calculated with Kaplan-Meier statistics. Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years, 55 to 69 years, and 70 to 85 years. Results: The 10-year risk of dementia was 0.27 (95% CI 0.20 to 0.34) in subjects with cognitive complaints, 0.28 (95% CI 0.21 to 0.35) in subjects with AACD, 0.44 (95% CI 0.32 to 0.56) in subjects with mild functional impairment, and 0.48 (95% CI 0.35 to 0.61) in subjects with amnestic MCI. Ninety-one percent of the demented subjects had probable AD. The risk of dementia increased with increasing age for all MCI definitions (p < 0.001). Depending on the MCI definition used, the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years, from 0.37 to 0.52 in subjects aged 55 to 69 years, and from 0.77 to 1.0 in subjects aged 70 to 85 years. Conclusions: The majority of subjects with MCI do not progress to dementia at the long term. Age strongly influences the dementia risk. MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects.

Ten-year risk of dementia in subjects with mild cognitive impairment. Authors' reply

Physical activity or appropriate exercise prevents the development of osteoporosis. However, the exact mechanism remains unclear although it is well accepted that exercise or mechanical loading regulates the hormones, cytokines, signaling pathways, and noncoding RNAs in bone. Accumulating evidence has shown that bone is a highly vascularized tissue, and dysregulation of vasculature is associated with many bone diseases such as osteoporosis or osteoarthritis. In addition, exercise or mechanical loading regulates bone vascularization in bone microenvironment via the modulation of angiogenic mediators, which play a crucial role in maintaining skeletal health. This review discusses the effects of exercise and its underlying mechanisms for osteoporosis prevention, as well as an angiogenic and osteogenic coupling in response to exercise.

/pdf/the-effect-of-exercise-on-the-prevention-of-osteoporosis-and-3it32x8fcq.pdf

The Effect of Exercise on the Prevention of Osteoporosis and Bone Angiogenesis

Recent advances in integrating microengineering and tissue engineering have enabled the creation of promising microengineered physiological models, known as organ-on-a-chip (OOC), for experimental medicine and pharmaceutical research. OOCs have been used to recapitulate the physiologically critical features of specific human tissues and organs and their interactions. Application of chemical and mechanical stimuli is critical for tissue development and behavior, and they were also applied to OOC systems. Mechanical stimuli applied to tissues and organs are quite complex in vivo, which have not adequately recapitulated in OOCs. Due to the recent advancement of microengineering, more complicated and physiologically relevant mechanical stimuli are being introduced to OOC systems, and this is the right time to assess the published literature on this topic, especially focusing on the technical details of device design and equipment used. We first discuss the different types of mechanical stimuli applied to OOC systems: shear flow, compression, and stretch/strain. This is followed by the examples of mechanical stimuli-incorporated OOC systems. Finally, we discuss the potential OOC systems where various types of mechanical stimuli can be applied to a single OOC device, as a better, physiologically relevant recapitulation model, towards studying and evaluating experimental medicine, human disease modeling, drug development, and toxicology.

Methods of Delivering Mechanical Stimuli to Organ-on-a-Chip.

Osteoporosis is a very common bone disorder characterized by low bone mass and signs of deterioration, responsible for bone fragility typical in this pathology. The risk factors for the onset of osteoporosis are many and different from each other. Some of them cannot be modified, such as age, hereditary diseases and endocrine diseases. Others are modifiable, so that prevention is an advisable tool to reduce the incidence of osteoporosis. Among preventive tools, physical activity is certainly a valid instrument of prevention, in fact physical activity contributes to a healthy energy balance and increases muscle mass and bone mass. In the present narrative review, we wanted to pay attention to the possible influence of physical activity on the pathophysiological molecular pathways of osteoporosis and to the use of different exercise training in treatment of osteoporosis. From the literature analyzed, in relation to the effects of physical activity on bone metabolism, it is shown that exercise acts on molecular pathways of bone remodeling involving all cellular types of bone tissue. In relation to clinical trials adopted in patients with osteoporosis, it is evident that a multi-component training, including aerobic activity and other types of training (resistance and/or strength exercises), is the best kind of exercise in improving bone mass and bone metabolism in older adults and especially osteopoenic and osteoporotic women. With regard to whole-body-vibration training, it seems to be a valid alternative to current methods due to its greater adaptability to patients. In conclusion, physical activity, whatever the adopted training, always has beneficial effects on patients suffering from osteoporosis, and not only on bone homeostasis but on the whole skeletal muscle system.

/pdf/the-importance-of-physical-activity-in-osteoporosis-from-the-3brgn4zxvy.pdf

The importance of physical activity in osteoporosis. From the molecular pathways to the clinical evidence

It is widely accepted that mechanical stress is an important factor in bone associated cell differentiation, including that of mesenchymal stem cells, osteoblasts and osteocytes. The present study aimed to determine the effect of mechanical cyclic compressive load on osteoblast differentiation, and whether this was associated with activation of the wingless‑type (Wnt)/β-catenin signaling pathway. Using a 3D scaffold model, MC3T3‑E1 cells were exposed to cyclic compressive loading via the Flexcell‑5000C™ Compression system. Sinusoidal wave magnitudes of 0.33, 0.5 and 1 MPa were applied for 4, 6 and 8 h, at 1 Hz frequency. Expression levels of genes associated with osteoblast differentiation were enhanced following compression, including alkaline phosphatase, osteocalcin, runt‑related transcription factor 2 and osterix. Optimal compression was observed using a magnitude of 0.5 MPa for 6 h, whereas a magnitude of 1 MPa had no effect on osteoblast differentiation, and had a negative effect when applied for prolonged time periods. Compressive loading additionally enhanced the mRNA expression levels of the Wnt/β‑catenin signaling pathway component, low density lipoprotein receptor‑related protein 5, and the protein expression levels of Wnt1, disheveled segment polarity protein‑2 (DVL2) and β-catenin. By contrast, mRNA expression levels of sclerostin and the inactive form of β-catenin (phosphorylated at Ser33/37/Thr41) were reduced following compressive loading. Following compressive loading of cells, dickkopf-related protein 1 (DKK‑1), an inhibitor of the Wnt signaling pathway, increased protein expression levels of the inactive form of the Wnt‑associated protein, phosphorylated‑β‑catenin, compared with compression alone. However, DVL2 and Wnt1 protein expression levels were unaffected, suggesting that the loading‑induced activation of Wnt/β‑catenin signaling decreased however, it was not prevented by DKK‑1 treatment. In conclusion, the present study demonstrated that cyclic compressive load promoted osteoblast differentiation and may be dependent on the Wnt/β-catenin signaling pathway in regard to magnitude and duration.

/pdf/cyclic-compression-stimulates-osteoblast-differentiation-via-3yvcw0pq7b.pdf

Cyclic compression stimulates osteoblast differentiation via activation of the Wnt/β-catenin signaling pathway.

With a rapid increase in the aging population, osteoporosis has become a global health problem. Although anti-resorption and anabolic drugs are available, osteoporosis cannot be completely cured. Exercise is an economical, efficacious, and safe way to prevent the development of osteoporosis. Recent studies have investigated the mechanisms by which exercise affects bone remodeling. Here we update the progress made on the effects of exercise on bone cells, including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts, as well as on bone mass, bone strength, and geometry, hoping to provide a theoretical basis to improve osteoporosis prevention and treatment with exercise.

The roles of exercise in bone remodeling and in prevention and treatment of osteoporosis.

Background: Mild cognitive impairment (MCI) is a brain disease with both anatomical and functional alterations. There is clear evidence that individuals that are diagnosed with MCI have a high risk to develop dementia in the next 2-5 years compared to an age-matched population with a non-MCI diagnosis. The present study aimed to investigate whether the finger tapping frequency of patients with MCI was different from that of healthy individuals without MCI, and whether Tai Chi, a traditional Chinese movement discipline, could improve the finger tapping frequency of MCI patients. Methods: The study population consisted of subjects of ≥50 years of age. Group one included 40 subjects without exercise habits from communities of Yangpu District in Shanghai, and group two included 60 subjects from a Tai Chi class in Shanghai Elderly University of Huangpu District. The Montreal Cognitive Assessment (MoCA) and a finger tapping test were conducted to assess the finger tapping frequency of all subjects. Results: The MoCA score of MCI subjects was significantly lower compared to subjects without MCI (P < 0.01), and was not influenced by age, weight, or height. The finger tapping frequency of MCI subjects' left hands was significantly lower compared to that of healthy subjects without MCI (P < 0.01), and a similar trend was observed for the subjects' right hand. The MoCA score of MCI subjects in the Tai Chi class was significantly lower than that of healthy subjects without MCI (P < 0.01), which was not influenced by age, weight or height. The finger tapping frequency of MCI subjects' right hands was lower compared to that of healthy subjects in the Tai Chi class without MCI (P < 0.05), but no significant difference regarding the finger tapping frequency of the left hand was observed. Conclusion: These findings suggested that finger tapping frequency of MCI subjects was significantly lower compared to normal subjects without MCI, and long-term Tai Chi exercise could reduce this significant difference. Moreover, there was no significant difference between groups for the subjects' non-dominant (left) hand.

/pdf/can-long-term-regular-practice-of-physical-exercises-51e6xgkekn.pdf

Can Long-Term Regular Practice of Physical Exercises Including Taichi Improve Finger Tapping of Patients Presenting With Mild Cognitive Impairment?

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Cyclic compression stimulates osteoblast differentiation via activation of the Wnt/β-catenin signaling pathway.

The roles of exercise in bone remodeling and in prevention and treatment of osteoporosis.

Can Long-Term Regular Practice of Physical Exercises Including Taichi Improve Finger Tapping of Patients Presenting With Mild Cognitive Impairment?