A cell's ability to recognize and adapt to the physical environment is central to its survival and function, but how mechanical cues are perceived and transduced into intracellular signals remains unclear. In mesenchymal stem cells (MSCs), high-magnitude substrate strain (HMS, ≥2%) effectively suppresses adipogenesis via induction of focal adhesion (FA) kinase (FAK)/mTORC2/Akt signaling generated at FAs. Physiologic systems also rely on a persistent barrage of low-level signals to regulate behavior. Exposing MSC to extremely low-magnitude mechanical signals (LMS) suppresses adipocyte formation despite the virtual absence of substrate strain (<0.001%), suggesting that LMS-induced dynamic accelerations can generate force within the cell. Here, we show that MSC response to LMS is enabled through mechanical coupling between the cytoskeleton and the nucleus, in turn activating FAK and Akt signaling followed by FAK-dependent induction of RhoA. While LMS and HMS synergistically regulated FAK activity at the FAs, LMS-induced actin remodeling was concentrated at the perinuclear domain. Preventing nuclear-actin cytoskeleton mechanocoupling by disrupting linker of nucleoskeleton and cytoskeleton (LINC) complexes inhibited these LMS-induced signals as well as prevented LMS repression of adipogenic differentiation, highlighting that LINC connections are critical for sensing LMS. In contrast, FAK activation by HMS was unaffected by LINC decoupling, consistent with signal initiation at the FA mechanosome. These results indicate that the MSC responds to its dynamic physical environment not only with “outside-in” signaling initiated by substrate strain, but vibratory signals enacted through the LINC complex enable matrix independent “inside–inside” signaling. Stem Cells 2013;33:2063–2076

Whole-body vibration (WBV) is an exercise modality or treatment/prophylaxis method in which subjects (humans, animals, or cells) are exposed to mechanical vibrations through a vibrating platform or device. The vibrations are defined by their direction, frequency, magnitude, duration, and the number of daily bouts. Subjects can be exposed while performing exercises, hold postures, sitting, or lying down. Worldwide, WBV has attracted significant attention, and the number of studies is rising. To interpret, compare, and aggregate studies, the correct, complete, and consistent reporting of WBV-specific data (WBV parameters) is critical. Specific reporting guidelines aid in accomplishing this goal. There was a need to expand existing guidelines because of continuous developments in the field of WBV research, including but not limited to new outcome measures regarding brain function and cognition, modified designs of WBV platforms and attachments (e.g., mounting a chair on a platform), and comparisons of animal and cell culture studies with human studies. Based on Delphi studies among experts and using EQUATOR recommendations, we have developed extended reporting guidelines with checklists for human and animal/cell culture research, including information on devices, vibrations, administration, general protocol, and subjects. In addition, we provide explanations and examples of how to report. These new reporting guidelines are specific to WBV variables and do not target research designs in general. Researchers are encouraged to use the new WBV guidelines in addition to general design-specific guidelines.

Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24), HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24), HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz) for 15 min/d (HU+VIB, n = 24), or served as age-matched controls (AC, n = 24). Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA), while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation.

Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities. The authors performed a narrative literature review of the possible mechanisms, and conducted a survey within the team to prioritize research and prevention approaches. Based on literature review the most likely cause for lumbar IVD herniations was concluded to be swelling of the IVD in the unloaded condition during spaceflight. For the cervical IVDs, the knowledge base is too limited to postulate a likely mechanism or recommend approaches for prevention. Basic research on the impact of (un)loading on the cervical IVD and translational research is needed. The highest priority prevention approach for the lumbar spine was post-flight care avoiding activities involving spinal flexion, followed by passive spinal loading in spaceflight and exercises to reduce IVD hyper-hydration post-flight.

Whole-body vibration (WBV) is a method utilizing vibrating platforms to expose individuals to mechanical vibration. In its various applications, it has been linked to improved muscular, skeletal, metabolic, or cognitive functioning, quality of life, and physiological parameters such as blood pressure. Most evidence concerning WBV is inconclusive and meta-analytical reviews may not readily produce insights since the research has a risk of misunderstandings of vibration parameters and incomplete reporting occurs. This study aims at laying an empirical foundation for reporting guidelines for human WBV studies to improve the quality of reporting and the currently limited comparability between studies. The Delphi methodology is employed to exploit the integrated knowledge of WBV experts to distil the specific aspects of WBV methodology that should be included in such guidelines. Over three rounds of completing online questionnaires, the expert panel (round 1/2/3: 51/40/37 experts respectively from 17 countries with an average of 19.4 years of WBV research experience) rated candidate items. A 40-item list was established based on the ratings of the individual items from the expert panel with a large final consensus (94.6%). The final consensus indicates comprehensiveness and valuableness of the list. The results are in line with previous guidelines but expand these extensively. The present results may therefore serve as a foundation for updated guidelines for reporting human WBV studies in order to improve the quality of reporting of WBV studies, improve comparability of studies and facilitate the development of WBV study designs.