The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States.

Bone homeostasis is a dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. This process is primarily controlled by the most abundant and mechanosensitive bone cells, osteocytes, that reside individually, within chambers of porous hydroxyapatite bone matrix. Recent studies have unveiled additional functional roles for osteocytes in directly contributing to local matrix regulation as well as systemic roles through endocrine functions by communicating with distant organs such as the kidney. Osteocyte function is governed largely by both biochemical signaling and the mechanical stimuli exerted on bone. Mechanical stimulation is required to maintain bone health whilst aging and reduced level of loading are known to result in bone loss. To date, both in vivo and in vitro approaches have been established to answer important questions such as the effect of mechanical stimuli, the mechanosensors involved, and the mechanosensitive signaling pathways in osteocytes. However, our understanding of osteocyte mechanotransduction has been limited due to the technical challenges of working with these cells since they are individually embedded within the hard hydroxyapatite bone matrix. This review highlights the current knowledge of the osteocyte functional role in maintaining bone health and the key regulatory pathways of these mechanosensitive cells. Finally, we elaborate on the current therapeutic opportunities offered by existing treatments and the potential for targeting osteocyte-directed signaling.

A survey of primary care physician referral to bariatric surgery in Manitoba: access, perceptions and barriers.

BACKGROUND: There is an important disconnect between surgical programs and primary care physicians (PCP) in the delivery of bariatric care. The objective of this study is to assess PCP knowledge and perception of a provincial bariatric surgery program. METHODS: A 32-question, IRB approved, survey was developed by bariatric surgery experts and vetted by local PCPs. A single round of paper surveys was administered to 1,000 PCPs between July and September 2015. Continuous variables were assessed by t-test and categorical variables by Chi-square test. RESULTS: There were 131 survey responses (13.1%). Half (54.2%) of respondents did not feel equipped to counsel their patients on operative management strategies. PCPs counselled on average 11.6%±17.0% of their obese patients on bariatric surgery. Many respondents (58.3%) thought excess weight loss from gastric bypass was less than 40% and most believed there was less than 50% resolution of diabetes (62.4%), hypertension (72.3%), dyslipidemia (77.8%) and obstructive sleep apnea (60.6%). PCPs who referred patients to the bariatric program (71.8%) were more comfortable counselling their patients on bariatric surgery options (56.8% vs. 17.1%, P<0.001) and were more comfortable with post-operative care (67.4% vs. 38.2%, P=0.004). Additionally, these PCPs estimated higher rates of diabetes and hypertension resolution post-bariatric surgery. The predominant perceived barrier to accessing bariatric surgery was wait times (33.3%). CONCLUSIONS: PCPs appear to underestimate the efficacy of bariatric surgery in the treatment of obesity and feel ill-equipped to counsel patients. Further education related to bariatric surgery may improve PCP comfort in counselling and long-term follow-up.

Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease.

A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease.