Marrow adipogenesis and bone loss that parallels estrogen deficiency is slowed by low-intensity mechanical signals

Krishnamoorthy, Divya; Frechette, Danielle M.; Adler, Benjamin J.; Green, D. E.; Chan, M. Ete; Rubin, Clinton T.

doi:10.1007/s00198-015-3289-5

Cited by 26 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…36,37 It is important to highlight that recent research has reported that repeated exposure to lowintensity vibration induced marked degeneration of murine knee joints, including meniscal tears and focal damage to the cartilage surface within the medial joint compartment. 38 From previous studies in our laboratory, 27,[39][40][41] we have not observed damage to connective tissues, whether bone, cartilage, tendon, IVD, muscle or ligament. Further, in clinical trials evaluating the capacity of LIV to preserve bone under conditions of disease or age, [42][43][44][45][46][47] no adverse event was reported relative to knee, hip or back pain.…”

Section: Low-intensity Vibration Increases Cartilage Thicknessmentioning

confidence: 54%

Low‐intensity vibration increases cartilage thickness in obese mice

Pamon

Bhandal

Adler

et al. 2017

Journal Orthopaedic Research

View full text Add to dashboard Cite

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 obesity. Five-week-old, male, C57BL/6 mice were separated into three groups (n = 10): Regular diet (RD), High fat diet (HF), and HF + LIV (HFv; 90 Hz, 0.2g, 30 min/d, 5 d/w) administered for 6 weeks. Additionally, an extended HF diet study was run for 6 months (LIV at 15 m/d). Articular cartilage and subchondral bone morphology, and sulfated GAG content were quantified using contrast agent enhanced μCT and histology. Gene expression within femoral condyles was quantified using real-time polymerase chain reaction. Contrary to our hypothesis, HF cartilage thickness was not statistically different from RD. However, LIV increased cartilage thickness compared to HF, and the elevated thickness was maintained when diet and LIV were extended into adulthood. RT-PCR analysis showed a reduction of aggrecan expression with high fat diet, while application of LIV reduced the expression of degradative MMP-13. Further, long-term HF diet resulted in subchondral bone thickening, compared to RD, providing early evidence of OA pathology-LIV suppressed the thickening, such that levels were not significantly different from RD. These data suggest that dynamic loading, via LIV, protected the retention of cartilage thickness, potentially resulting in joint surfaces better suited to endure the risks of elevated loading that parallel obesity. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:751-759, 2018.

show abstract

Section: Low-intensity Vibration Increases Cartilage Thicknessmentioning

confidence: 54%

Low‐intensity vibration increases cartilage thickness in obese mice

Pamon

Bhandal

Adler

et al. 2017

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…However, excessive BMAT accumulation is also observed following diverse clinical conditions such as exposure to radiation, chemotherapy, and glucocorticoid treatment, or following starvation, as in patients with anorexia nervosa . Furthermore, lifestyle influences (such as unloading of bones, seen in astronauts or during extensive bedrest) and obesity can also increase BMAT, whereas exercise and mechanical stimulation can decrease BMAT . Exercise may reduce BMAT by enhancing energy expenditure and FA β‐oxidation …”

Section: Bone Marrow Adipose Tissuementioning

confidence: 99%

Multiple Myeloma and Fatty Acid Metabolism

et al. 2019

View full text Add to dashboard Cite

Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown, and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts. MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive‐feedback “vicious cycle” between MM cells and osteoclasts that leads to bone resorption and tumor proliferation. Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored. Given their active endocrine function, capacity for direct cell–cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells. This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

show abstract

“…These studies showed that LIV (0.2–0.3 × g , 90Hz, 15–30 min/day) was able to partially protect against estrogen-deficient bone loss and reduce the presence of adipocytes or adipogenic gene expression in bone marrow and muscle tissues. 70,174 …”

Section: Combating Obesity With Mechanical Signalsmentioning

confidence: 99%

“…63 MSC differentiation is also regulated by the Wnt signaling pathway, [64][65][66] and it is understood that osteoblastogenesis and adipogenesis in the marrow generally maintain an inverse relationship. Adipocyte commitment is often associated with reduced bone formation, as seen in models of microgravity, 67,68 ovarian hormone depletion, 69,70 and aging. 71 Through Wnt signaling or other osteogenic signaling pathways, it is plausible that MSC commitment to adipogenesis in the obese state can be controlled.…”

Section: The Bone Marrow Is a Dynamic Heterogeneous Environment And Hmentioning

confidence: 99%

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

Frechette

Krishnamoorthy

Pamon

et al. 2017

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type 2 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 function. The complexity of obesity makes understanding the etiology of bone and muscle abnormalities difficult. Exercise is an effective and commonly prescribed non-pharmacological treatment option, but it can be difficult or unsafe for the frail, elderly, and morbidly obese. Exercise alternatives, such as low-intensity vibration (LIV), have potential for improving musculoskeletal health, particularly in conditions with excess fat. LIV has been shown to influence bone marrow mesenchymal stem cell differentiation toward higher-order tissues (i.e., bone) and away from fat. While the exact mechanisms are not fully understood, recent studies utilizing LIV both at the bench and in the clinic have demonstrated its efficacy. Here, we discuss the current literature investigating the effects of obesity on bone, muscle, and bone marrow and how exercise and LIV can be used as effective treatments for combating the negative effects in the presence of excess fat.

show abstract

Marrow adipogenesis and bone loss that parallels estrogen deficiency is slowed by low-intensity mechanical signals

Cited by 26 publications

References 43 publications

Low‐intensity vibration increases cartilage thickness in obese mice

Low‐intensity vibration increases cartilage thickness in obese mice

Multiple Myeloma and Fatty Acid Metabolism

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity

Contact Info

Product

Resources

About