Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-Cl- cotransporters.

Bone turnover diseases are exceptionally prevalent in human and come with a high burden on physical health. While these diseases are associated with a variety of risk factors and causes, they are all characterized by common denominators, that is, abnormalities in the function or number of osteoblasts, osteoclasts, and/or osteocytes. As such, much effort has been deployed in the recent years to understand the signaling mechanisms of bone cell proliferation and differentiation with the objectives of exploiting the intermediates involved as therapeutic preys. Ion transport systems at the external and in the intracellular membranes of osteoblasts and osteoclasts also play an important role in bone turnover by coordinating the movement of Ca2+ , PO4 2- , and H+ ions in and out of the osseous matrix. Even if they sustain the terminal steps of osteoformation and osteoresorption, they have been the object of very little attention in the last several years. Members of the cation-Cl- cotransporter (CCC) family are among the systems at work as they are expressed in bone cells, are known to affect the activity of Ca2+ -, PO4 2- -, and H+ -dependent transport systems and have been linked to bone mass density variation in human. In this review, the roles played by the CCCs in bone remodeling will be discussed in light of recent developments and their potential relevance in the treatment of skeletal disorders.

Inter-segmental coordination amplitude and variability differences during gait in patients with Ehlers-Danlos syndrome and healthy adults.

BACKGROUND: There is limited research examining gait and inter-segmental coordination in patients with Ehlers-Danlos syndrome. The objective was to compare lower extremity inter-segmental coordination amplitude and variability during gait between patients with Ehlers-Danlos syndrome and healthy adults. METHODS: This cross-sectional study included participants with Ehlers-Danlos syndrome (n = 13) and healthy adults (n = 14). Gait data were acquired using a motion capture system and force plates. Participants ambulated at self-selected speeds for five trials. Inter-segmental coordination was quantified using continuous relative phase, which examined the dynamic interaction between the thigh-shank and shank-foot paired segments (i.e. phase space relation). A 2-way mixed analysis of variance examined the effects of groups (Ehlers-Danlos and healthy) and gait phases (stance and swing phase) on inter-segmental coordination amplitude and between-trial variability. Effect sizes were calculated using Cohen's d. FINDINGS: The Ehlers-Danlos group had greater inter-segmental coordination variability compared to the healthy group for foot-shank and shank-thigh segment pairs in the sagittal plane over stance and swing phases (P = 0.04; small to large effect sizes). The Ehlers-Danlos group also had greater variability in the frontal plane at the foot-shank segment pair during stance phase (P = 0.03; large effect). There were no differences in inter-segmental coordination amplitude between groups (P = 0.06 to 0.85). INTERPRETATION: Patients with Ehlers-Danlos syndrome have more variability between gait trials in lower limb motor coordination than healthy adults. This may be related to the impaired proprioception, reduced strength, pain, or slower gait speed seen in this population.