Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?

Hind, Karen; Jones, Ben; King, Rhodri

doi:10.1055/s-0034-1372585

Cited by 2 publications

(4 citation statements)

References 8 publications

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“…2). Their ability to migrate to the site of injury (homing capacity) is based on the presence of chemokine receptors that respond to chemokine attractive gradients generated by the injured tissue [21]. These more recently identified BMSSCs properties have led to an expansion of possible therapeutic applications, where a significant role is for them to enhance the intrinsic regenerative capacity of compromised tissues through modulation of the immune response, inflammation, and the concentration of growth factors in the local microenvironment [17].…”

Section: Reviewmentioning

confidence: 99%

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Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine

2016

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Bone marrow stromal stem cells (BMSCs) are adult multipotent cells, which have the potential to differentiate into cell types of mesodermal origin, namely osteocytes, adipocytes, and chondrocytes. Due to their accessibility and expansion potential, BMSCs have historically held therapeutic promise in tissue engineering and regenerative medicine applications. More recently, it has been demonstrated that not only can bone marrow stromal stem cells directly participate in tissue regeneration, but they also have the capacity to migrate to distant sites of tissue injury, where they can participate in tissue repair either directly through their differentiation or indirectly through paracrine mechanisms. Additionally, they can elicit various immunomodulatory signals, which can attenuate the inflammatory and immune responses. As such, bone marrow stromal stem cells have been explored clinically for treatment of a wide variety of different conditions including bone defects, graft-vs.-host disease, cardiovascular diseases, autoimmune diseases, diabetes, neurological diseases, and liver and kidney diseases. This review provides an overview of current clinical applications of bone marrow stromal stem cells and discusses their therapeutic properties, while also addressing limitations of their use. PubMed, Ovid, and Google Scholar online databases were searched using several keywords, including "stem cells", "tissue engineering", tissue regeneration" and "clinical trials". Additionally, Clinical trials.gov was used to locate completed clinical trials using bone marrow derived stem cells.

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Section: Reviewmentioning

confidence: 99%

“…Bone is a metabolically active tissue which continuously undergoes the process of resorption and formation through highly coordinated processes controlled by multiple factors [19][20][21]. When subjected to trauma or damage, bone has the innate selflimiting capacity to repair small fractures and non-"criticalsized" defects.…”

Section: Musculoskeletal Conditionsmentioning

confidence: 99%

Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine

2016

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“…We appreciate the substantive body of evidencebased research that defi nitely supports low energy availability as the primary driver of athletic osteopenia, as pointed out by Hind et al in their letter [ 1 ] . However, we wish to emphasize that prolonged endurance exercise represents an accelerated physiological model for which shortrange (nongenomic) regulatory circuits likely become more operative [ 2 -5 ] .…”

Section: Dear Editorsmentioning

confidence: 84%

“…Despite these limitations and uncertainties, we feel that our results provide insights into the intersection of sodium balance, bone metabolism, and exercise physiology, particularly with regard to the potential importance of short-range homeostatic circuits. Only additional studies employing larger numbers of subjects and suffi ciently sensitive technologies will resolve the issues raised by Hind et al [ 1 ] .…”

Section: Dear Editorsmentioning

confidence: 99%

Reply to Letter to the Editor by Hind et al.

2014

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Dear Editors, We appreciate the substantive body of evidencebased research that defi nitely supports low energy availability as the primary driver of athletic osteopenia, as pointed out by Hind et al. in their letter [ 1 ] . However, we wish to emphasize that prolonged endurance exercise represents an accelerated physiological model for which shortrange (nongenomic) regulatory circuits likely become more operative [ 2 -5 ] . Heightened physiological and mental stress necessitates momentto-moment short-loop homeostatic responses that serve to complement the more classic genomic model of steroid activation, which takes hours to days to fully initiate [ 2 ] . As such, the metabolic demands of running a 161 km footrace in less than 30 h are 10-fold higher (13 000-16 000 kcal/day [ 6 ] ) than the estimated basal metabolic rate of our 6 race fi nishers (1 531 kcal/ day, using the Harris-Benedict Equation [ 7 ] ). Thus, our data do not in any way undermine the classic physiological processes that contribute to low bone mineral density chronically in endurance athletes, but seek to build upon existing data to further determine whether or not: 1) pituitary-bone short-range homeostatic circuits exist and if so, 2) does repetitive stimulation of such short-range circuits have long-term pathological consequences related to low energy and serum mineral availability? Short-range regulatory circuits linking sodium and bone metabolism have been previously demonstrated, but in isolated contexts. For example, the nongenomic eff ects of aldosterone have been shown to activate the epithelial sodium channel in animal models [ 8 ] . Additionally, rapid increases in plasma aldosterone concentrations have been confi rmed after only 10 min of high intensity exercise in humans, presumably from a nongenomic source [ 9 ] . Arginine vasopressin receptors type 1α (AVPR1α) and type 2 (AVPR2) have also been shown to exist on osteoblasts and osteoclasts, with short-circuit AVP stimulation favoring overall bone resorption in mouse models [ 3 ] . Similarly, exercise-induced nonosmotic plasma AVP concentrations have been verifi ed in humans and could hypothetically translate into acute bone remodeling if exercise duration and elevated plasma AVP levels were sustained [ 9 ] . Lastly, the heteroionic exchange of ions within the hydration shell of bone -and across the 80 % of quiescent osteoblasts present in the skeleton -can liberate 50-100 mmol of calcium daily from the skeleton to acutely regulate serum calcium levels without activation of the classic remodeling mechanisms [ 4 ] . Thus, the ability of hydroxyapatite crystals to dynamically mirror the composition of the surrounding extracellular fl uid has been shown to be physicochemically plausible [ 4 ] . Whether or not these short-circuit homeostatic responses could potentially lead to irreversible pathology over time (such as in the osteoporosis case documented in a middle aged male with chronic inappropriate AVP secretion) [ 10 ] , remains uncertain. Systematic investigations aimed at verifyi...

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Re: Bone: An Acute Buffer of Plasma Sodium During Exhaustive Exercise?

Cited by 2 publications

References 8 publications

Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine

Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine

Reply to Letter to the Editor by Hind et al.

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