Make No Bones About It: Environmental Contaminants Impact Bone Formation and the Immune System
By Amelia Haas, MD/PhD Candidate
Graduate Program in Molecular Medicine
Boston University School of Medicine
This article is in the series "From Research to Real Life" that GBPSR presents in conjunction with the Boston University Superfund Research Program (BUSRP).
We hope this information encourages you to become more involved in PSR programs or other activities that address preventing toxic exposures that may jeopardize public health.
Changes as We Age
Our skeleton, made up of 206 bones, serves a myriad of functions - giving our bodies form, supporting movement, protecting vital organs, storing vital minerals like calcium, phosphorus, and iron, and producing blood cells. The interior of bones, called bone marrow, is made of cells that produce bone (osteoblasts), cells that break down bone (osteoclasts), fat cells (adipocytes), and cells that will develop into infection-fighting immune cells (lymphocytes). During the aging process, the bone marrow becomes fatty and bones become more susceptible to fracture. The pathological end of this progression is the well-known disease, osteoporosis. Aging also is associated with a loss of immune cells and a reduced ability to respond to infection, which parallels the increase in fat formation in the bone marrow.
Our immune system largely develops in and is supported by the bone marrow. Over our lifespan, our immune system, like our skeleton, is weakened. This is demonstrated by a reduced ability to make new white blood cells called B lymphocytes, which are responsible for defending our body against bacteria and fungi. The function of another white blood cell, the T lymphocyte, also decreases with age. T lymphocytes are responsible for defending our body against viruses. Changes in the immune system, especially the reduced capacity to generate B lymphocytes, may be associated with and at least in part caused by the changes in the bone marrow that support their development. Recent literature shows that bone producing cells, which decrease with age, are necessary for B lymphocyte development and that fat cells, which increase with age, impair B lymphocyte development.
While obesity in general is a risk factor for many chronic diseases, including diabetes, cardiovascular disease, and certain cancers, extra fat inside our bones appears to be a risk factor for osteoporosis and an impaired immune system. Although this increase in fat in our bone marrow occurs during the normal aging process, we wonder if exposure to environmental contaminants accelerates and/or exacerbates aging-associated changes.
Organotin Exposure and Impact
In 2006, Dr. Bruce Blumberg and colleagues coined the term "environmental obesogen" referring to a group of contaminants that promote an increase in fatty tissues. These chemicals are thought to work as obesogens because of their ability to interact with a protein receptor (peroxisome proliferator activated receptor , PPAR ) that controls formation of fat cells (adipocytes). When environmental contaminants bind to this protein receptor, fat formation is stimulated at many sites within the body. While perhaps an unexpected site of fat formation, we are interested in how these obesogens increase fat content in bone. Other chemicals, such as a drug called rosiglitazone (which is used to treat Type 2 Diabetes), also bind to PPAR and promote the expansion of fat cells. In people being treated with rosiglitazone, it has been shown that this medication affects the bone marrow by increasing the amount of fat and decreasing bone integrity.
Where is this risk coming from? Two major groups of ubiquitous environmental contaminants, phthalates and organotins, are suggested to be obesogens. Phthalates are a well-known contaminant of plastics. For decades, organotins have been a contaminant of concern in the marine environment due to its use as an anti-fouling agent; however the use of these compounds in agricultural pesticides, wood preservatives and the manufacturing of plastics has resulted in significant land-based sources of this environmental contaminant. One organotin, tributyltin (TBT), is very potent at promoting fat cell development. Our lab, as well as others, have shown this increase in fat can happen in laboratory experiments at very low concentrations, concentrations that have been measured in human liver and blood.
Past work in our lab shows that environmentally relevant, low levels of TBT are directly toxic to developing B lymphocytes in laboratory cultures. Our current research focuses on how TBT, at the same or even lower concentrations, may also negatively affect B lymphocytes by altering their supportive environment, the bone marrow. Additionally, we are interested in how TBT may accelerate the degradation of bone associated with aging. We are currently investigating how these low doses of TBT lead to an increase in fat production and a decrease in bone production, and, in turn, impact the developing immune system. Collectively, our studies will contribute to both the basic understanding of how environmental contaminants alter the bone marrow leading to premature aging, and also give new insight into how exposure to chemicals, both environmental and in the form of medication, affect the interrelationship between immune cells and the bone marrow.
Ms. Haas works in the laboratory of Dr. Jennifer Schlezinger and Dr. David Sherr. Dr. Schlezinger's primary appointment is in the Department of Environmental Health in the Boston University School of Public Health. She is also a faculty member in the Immunology Training Program and the Graduate Program in Molecular Medicine. Dr. Sherr holds joint appointments in the Department of Environmental Health and in the Department of Pathology and Laboratory Medicine in the Boston University School of Medicine.