Clinton Rubin

Clinton Rubin
Stony Brook University | Stony Brook · Department of Biomedical Engineering

Ph.D.

About

375
Publications
48,669
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
24,682
Citations
Introduction
Driving Mesenchymal Stem Cell Fate by Low Intensity Mechanical Signals as a Non-Drug Treatment for Osteoporosis and Obesity Research shows that low level strains to animals and humans will increase bone formation, and thus may represent a non-drug "anabolic" stimulus to the musculoskeletal system. These low-level signals also influence mesenchymal stem cell differentiation, suppressing adipogenesis , and reduces adipose tissue, representing a strategy for treatment of obesity and diabetes.
Additional affiliations
January 1987 - December 2012
Stony Brook University
January 1987 - present
State University of New York
Position
  • SUNY Distinguished Professor and Chair
January 1984 - December 1986
Tufts University

Publications

Publications (375)
Article
Full-text available
The ability of low intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height‐adjusted Z‐scores (HAZ) of hip BMD ‐2.3). Ten DMD boys were assigned to stand for 10min/d on a...
Preprint
Full-text available
Introduction/Aims The ability of low intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Methods Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height-adjusted Z-scores (HAZ) of hip BMD −2.3). Ten DMD boys were assigne...
Article
Full-text available
Background The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects...
Article
Full-text available
Background The prevailing medical opinion is that medication is the primary (some might argue, only) effective intervention for osteoporosis. It is nevertheless recognized that osteoporosis medications are not universally effective, tolerated, or acceptable to patients. Mechanical loading, such as vibration and exercise, can also be osteogenic but...
Article
Aging induces alterations in bone structure and strength through a multitude of processes, exacerbating common aging- related diseases like osteoporosis and osteoarthritis. Cellular hallmarks of aging are examined, as related to bone and the marrow microenvironment, and ways in which these might contribute to a variety of age-related perturbations...
Chapter
The sophisticated organisation of the skeleton achieves a structure that can withstand the extremes of functional load-bearing. The growth, development and repair of the skeletal structure are realised through the tightly regulated remodelling of bone tissue, orchestrated by cells that specifically form or resorb the matrix. Diseases such as osteop...
Article
Patients afflicted with or being treated for cancer constitute a distinct and alarming subpopulation who exhibit elevated fracture risk and heightened susceptibility to developing secondary osteoporosis. Cancer cells uncouple the regulatory processes central for the adequate regulation of musculoskeletal tissue. Systemically taxing treatments to ta...
Preprint
Full-text available
Background The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects...
Article
Full-text available
Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms th...
Article
Full-text available
Introduction: Globally, 300 million adults have clinical obesity. Heightened adiposity and in- adequate musculature secondary to obesity alter bipedal stance and gait, diminish musculo- skeletal tissue quality, and compromise neuromuscular feedback; these physiological chang- es alter stability and increase injury risk from falls. Studies in the fi...
Preprint
Full-text available
Exercise benefits the musculoskeletal system and reduces the effects of cancer. The beneficial effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the me...
Article
Full-text available
Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications a...
Article
Full-text available
Background: Osteoporosis parallels aging and functional mechanical unloading (e.g., space flight and bed rest), jeopardizing mineral density, microstructure, and integrity of bone and leading to an increased risk of fracture. A way to combat this deterioration is to harness the sensitivity of bone to mechanical signals. Objective: This study eva...
Article
Full-text available
PURPOSE OF REVIEW: Changes in the bone marrow microenvironment, which accompany aging and obesity, including increased marrow adiposity, can compromise hematopoiesis. Here we review deleterious shifts in molecular, cellular and tissue activity, and consider the potential of exercise to slow degenerative changes associated with aging and obesity. R...
Patent
Full-text available
Article
Full-text available
Obesity is associated with an elevated risk of osteoarthritis (OA). We examined here whether high fat diet administered in young mice, compromised the attainment of articular cartilage thickness. Further, we sought to determine if low intensity vibration (LIV) could protect the retention of articular cartilage in a mouse model of diet induced obesi...
Article
Full-text available
Objective: To determine whether inclusion of a refractory period between bouts of low magnitude mechanical stimulation (LMMS) can curb obesity-induced adipose tissue dysfunction and sequelae in adult mice. Methods: A diet-induced obesity model with 45kcal% fat diet was employed with intention-to-treat. C57BL/6J mice were weight-matched into four...
Article
Full-text available
The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type II diabetes, heart disease, fatty liver disease, and cancer. The impact of excess fat on musculoskeletal health is still unclear, although it is associated with increased fracture risk and a decline in muscular funct...
Article
Full-text available
Rational and Objectives Low intensity vibration (LIV) may represent a nondrug strategy to mitigate bone deficits in patients with end-stage renal disease. Materials and Methods Thirty end-stage renal patients on maintenance hemodialysis were randomized to stand for 20 minutes each day on either an active or placebo LIV device. Analysis at baseline...
Article
Full-text available
The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated-MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO n = 14) vs. low-fat diet (LFD n = 14)....
Article
Traditionally associated with negative effects on the human body, paradoxically, vibration is now being used to treat certain medical conditions and even protect astronauts from the physical effects of long-duration spaceflight. Here, an invited panel of experts reviews current evidence for vibration, examining its effectiveness and appropriateness...
Article
Full-text available
A recent posting for a tenure-track junior faculty position in my department attracted over 200 applications, a frightening number in and of itself. Perhaps more terrifying, however, was that fewer than 5% of these submissions made any effort whatsoever to communicate why they wanted to join our faculty in particular. The cover letters—essentially...
Article
Full-text available
We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health. In...
Article
Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibrations (LIV), a component of mechanical signaling, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n = 25) were injected with human-myeloma cells, while 8 (AC) w...
Article
Full-text available
Mechanoresponses in mesenchymal stem cells (MSCs) guide both differentiation and function. In this review, we focus on advances in our understanding of how the cytoplasmic cytoskeleton, nuclear envelope, and nucleoskeleton, which are connected via linker of nucleoskeleton and cytoskeleton (LINC) complexes, are emerging as an integrated dynamic sign...
Article
Full-text available
Pediatric Crohn's Disease (CD) is associated with low trabecular bone mineral density (BMD), cortical area, and muscle mass. Low magnitude mechanical stimulation (LMMS) may be anabolic. We conducted a 12 month randomized double-blind placebo-controlled trial of 10 minutes daily exposure to LMMS (30 Hz frequency, 0.3 g peak to peak acceleration). Th...
Article
Full-text available
Background: Deficits in balance and muscle function are important risk factors for falls in older adults. Aging is associated with significant declines in muscle size and density, but associations of trunk muscle size and density with balance and falls in older adults have not been previously examined. Methods: Trunk muscle size (cross-sectional...
Article
Full-text available
Force magnitudes have been suggested to drive the structural response of bone to exercise. As importantly, the degree to which any given bone can adapt to functional challenges may be enabled, or constrained, by regional variation in the capacity of marrow progenitors to differentiate into bone-forming cells. Here, we investigate the relationship b...
Conference Paper
Full-text available
Introduction: Obesity, making up 35.7% of American population (Ogden, et al., 2012), causes weaker bones and higher bone fracture susceptibility. Our previous study showed that low-intensity vibrations (LIVs) can increase the effective mechanical strength in cortical shells of diet-induced obese mice. Yet, how the material and distribution of mecha...
Article
Full-text available
Ovariectomized mice were used to assess the ability of low-intensity vibrations to protect bone microarchitecture and marrow composition. Results indicate that low-intensity vibrations (LIV), introduced 2 weeks postsurgery, slows marrow adipogenesis in OVX mice but does not restore the bone within the period studied. However, immediate application...
Article
Full-text available
Force magnitudes have been suggested to drive the structural response of bone to exercise. As importantly, the degree to which any given bone can adapt to functional challenges may be enabled, or constrained, by regional variation in the capacity of marrow progenitors to differentiate into bone-forming cells. Here, we investigate the relationship b...
Article
Full-text available
The contribution of marrow adipose tissue (MAT) to skeletal fragility is poorly understood. PPARγ agonists, associated with increased fractures in diabetic patients, increase MAT. Here we asked if exercise could limit the MAT accrual and increase bone formation in the setting of PPARγ agonist treatment. Eight week-old female C57BL/6 mice were treat...
Article
Full-text available
Age-related degeneration of the musculoskeletal system, accelerated by menopause, is further complicated by increased systemic and muscular adiposity. The purpose of this study was to identify at the molecular, cellular, and tissue levels, the impact of ovariectomy on adiposity and satellite cell populations in mice, and whether mechanical signals...
Article
Full-text available
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 (MSC), high magnitude substrate strain (HMS, ≥2%) effectively suppresses adipogenesis via induction of FAK/mTORC2/Akt...
Article
Full-text available
Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors rec...
Article
Full-text available
Obesity markedly increases susceptibility to a range of diseases and simultaneously undermines the viability and fate selection of haematopoietic stem cells (HSCs), and thus the kinetics of leukocyte production that is critical to innate and adaptive immunity. Considering that blood cell production and the differentiation of HSCs and their progeny...
Conference Paper
Full-text available
Introduction Percutaneous, skeletally anchored implants eliminate the load-bearing skin-socket interface and should be associated with reduced morbidity as compared with traditional stump-socket prostheses. However, long-term success of these implants depends on stable osseointegration. Low-intensity vibration (LIV) increases bone density in vivo b...
Article
Full-text available
The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decl...
Article
Full-text available
Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminis...
Article
Full-text available
The bone marrow (BM) niche is the primary site of hematopoiesis, and cues from this microenvironment are critical to maintain hematopoiesis. Obesity increases lifetime susceptibility to a host of chronic diseases, and has been linked to defective leukogenesis. The pressures obesity exerts on hematopoietic tissues led us to study the effects of a hi...
Article
Full-text available
Microgravity induced bone loss represents a critical health problem in astronauts, particularly occurred in weight-supporting skeleton, which leads to osteopenia and increase of fracture risk. Lack of suitable evaluation modality makes it difficult for monitoring skeletal status in long term space mission and increases potential risk of complicatio...
Article
Full-text available
Exercise in general, and mechanical signals in particular, help ameliorate the neuromuscular symptoms of aging and possibly other neurodegenerative disorders by enhancing muscle function. To better understand the salutary mechanisms of such physical stimuli, we evaluated the potential for low intensity mechanical signals to promote enhanced muscle...
Article
Full-text available
Poor balance in older persons contributes to a rise in fall risk and serious injury, yet no consensus has developed on which measures of postural sway can identify those at greatest risk of falling. Postural sway was measured in 161 elderly individuals (81.8y±7.4), 24 of which had at least one self-reported fall in the prior six months, and compare...
Chapter
Osteopenia, a condition of diminished bone mass, becomes osteoporosis when mechanical demands exceed the ability of the skeletal structure to support them. Mechanical signals generated by exercise can mitigate bone loss as well as help preserve the musculoskeletal “system.” The physical and/or biologic basis of how mechanical signals are transforme...
Article
Stephen Jay Gould's commentary on Darwinism emphasizes the vital importance of an organism's ability to adapt effectively to changing signals arising from the environment. Pressure, gravity, waves, temperature, light, electric, and magnetic fields make up an omnipresent physical presence since the beginning of time. It should be no surprise, theref...
Article
Full-text available
Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the ‘biologically orchestrated’ resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice expos...