Posts Tagged ‘mechanosensitive’

Author: Aviral Vatsa, Ph.D., MBBS

Bone is a highly dynamic tissue that responds to changes in its external environment. Our bones adapt their mass and architecture according to the external mechanical loading conditions. Any long term alterations in loading conditions result in alteration of bone mass and architecture. This is highlighted in the following examples:

  1. Astronauts tend to lose their bone when they are in space. This is because the bones are not mechanically loaded externally due to absence of or reduction in gravitational force.
  2. Tennis players gain more mass in their playing forearm as compared to the non-playing forearm.

In both these examples bones tend to readjust their internal structural mass and alignment as per the external loads or their absence. How bones can achieve this? How bone forming and bone resorbing cells can be orchestrated to bring about this adaptation?

Bone cells

The questions mentioned above can be answered by knowing more about the cellular components of bone and their functions. Our bones primarily have four cell types: osteocytes, osteoblasts, osteoclasts and bone lining cells. Osteocytes are believed to be the ‘professional’ mechanosensors of bone i.e. they sense the external loads put on bone. Osteoblasts are the bone forming cells. Osteoclasts are the bone resorbing cells and as the name suggests, bone lining cells line the bone surfaces and play a role in regeneration of osteogenic cells. Osteocytes, following mechanical loading, secrete signalling molecules such as nitric oxide (besides others). These signalling molecules then modulate the activity of bone forming osteoblasts and/or bone resorbing osteoclasts. Thus osteocytes orchestrate this process wherein adequate bone mass and architecture is achieved in accordance with the external loading conditions.

Anatomically, the osteocytes reside with in the hard bony matrix. They are the majority cell types in bone and are ideally placed to sense the mechanical loads. Osteocytes have a cell body and from the cell body arise nearly fifty cell processes. Through these cell processes each osteocyte forms a network with the surrounding osteocytes. Through this network, following mechanical loading, osteocytes can stimulate the activity of osteoblasts and inhibit the activity of osteoclasts. This process of maintenance of bone mass and architecture is called bone remodelling. Bone remodelling occurs through out our life. It occurs in response to microfractures, which can appear in our bone without being noticed clinically. As long as our bone metabolism is physiologically normal these stimuli, such as microfractures, result in bone remodelling.

In diseases such as osteoporosis, the mechanism of bone remodelling is disrupted and there is more bone resorbtion than new bone formation thus leading to reduction in bone mass and alteration of bone architecture. Drug therapies for osteoporosis such as bisphosphonates, act by inhibiting the activity of osteoclasts thereby resulting in reduction in bone resorbtion and hence helping in maintenance of adequate bone mass and architecture. Newer therapies that target to modulate a part of bone remodelling are being investigated.

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Cancer and Bone: low magnitude vibrations help mitigate bone loss

Curator and Reporter: Ritu Saxena, Ph.D.

Recently, an article published in the journal Bone described that the low magnitude vibrations might be helpful in mitigating osteopenia in spontaneous granulosa cell ovarian cancer.

Osteopenia is defined as the bone mineral density (BMD) that is lower than normal peak BMD but not low enough to be classified as the diseased condition called osteoporosis. Bone mineral density is a measurement of the level of minerals in the bones, that shows how dense and strong they are. Having osteopenia means there is a greater risk that, as time passes, you may develop BMD that is very low compared to normal, known as osteoporosis

Cancer progression is often paralleled by a decline in bone mass, raising risk of fracture. Loss in bone mass can be therapeutically treated by using bone anabolic agents that increase the process of bone formation compared to bone resorption thus leading to an overall increase in bone mass. However, use of anabolic agents for preventing cancer associated bone loss presents a lot of concern as they may exacerbate cancer tissue expansion.

Bone is a mechanosensitive organ. Osteoblastogenesis, or the process of differentiation of precursor cells to bone forming cells (osteoblasts) is encouraged by low intensity vibration (LIV) via a mechanical signal. Rubin et al explored the possibility of slow cancer-associated bone loss, but this goal must be achieved without fostering disease progression. The hypothesis was tested in the murine model.

Seventy female F1-SWRxSWXJ-9 mice, a strain prone to developing granulosa cell tumors, were divided into three groups – baseline control (BC: n=10), age-matched control (AC: n=30), and LIV (n=30), which received mechanical signals (90Hz @ 0.3g) for 15m/day, 5day/w over the course of 1year. Survival curves observed in the three groups indicated that longevity was unperturbed by LIV. Rubin et al stated that “1year, bone volume of proximal tibiae in LIV mice was 25% greater than AC while bone volume of L5 vertebrae was 16% higher in LIV over AC (p<0.02). Primary lesions and peripheral metastases were apparent in both LIV and AC; however, overall tumor incidence was approximately 30% less in LIV (p=0.27) and, when disease was evident, involved fewer organ systems (p=0.09).”

These experiments indicate that LIV helps protect bone mass in mice inherently susceptible to cancer without compromising life expectancy, perhaps through mechanical control of stem cell fate. Further, these data reflect the numerous system-level benefits of exercise in general, and mechanical signals in particular, in the preservation of bone density and the suppression of cancer progression.

Source: Journal article- http://www.thebonejournal.com/article/S8756-3282(12)00867-8/abstract, http://www.webmd.com/osteoporosis/tc/osteopenia-overview

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