A Novel Method to Manipulate Osteoblastic Differentiation

Osteoporosis is the thinning of bone tissue and loss of bone density over time, leading to an increased risk of fracture. This prevalent bone disease results when bone, a living tissue, fails to form enough new bone while the existing bone is reabsorbed by the body at a greater rate. Since mammals have limited regenerative ability, the lack of production of new bone as a result of this disease is extremely problematic. Primary osteoporosis is genetic, but secondary osteoporosis can result from smoking, alcohol, lack of exercise, intake of steroids and certain medications. Of interest in developing a cure for osteoporosis, is the ability to manipulate osteoblast differentiation. Osteoblasts are specialized mesenchymal cells that are responsible for bone formation through their differentiation process. The remodeling and maintenance of the bone tissue is reliant on the balance between the processes of bone resorption and bone formation. Osteoblasts are responsible for the formation of bone, while osteoclasts are responsible for reabsorption of bone [1]. Osteoblast differentiation in vivo occurs in three steps. The first step is cell proliferation; the second step is matrix maturation; and the final step is matrix mineralization. Alkaline phosphatase (ALP) levels reach their peak at the maturation phase of the differentiation process. This characteristic indicates that a decrease in ALP represents the movement from maturation to either proliferation or mineralization. The proliferation and mineralization phases of the differentiation process are characterized by the presence of certain proteins; procollagen I, TGF-beta, and fibronectin in the proliferation stage and osteocalcin, bone sialoprotein, osteopontin and inorganic mineral hydroxylapatite in the mineralization phase [2]. TGF-beta acts as a mitogen for osteoblast cells, aiding in the prompting of cells to go through mitosis [3]. Since osteoblasts are responsible for bone formation, both the proliferation and mineralization phases of the differentiation process are essential to strengthening of bone in patients with osteoporosis. Thus, manipulation of this differentiation process could provide mechanisms for reverting differentiation back to the proliferation stage, or continuation to the mineralization stage to further strengthen bone development. It has been shown that zeolite, a microporous mineral with a variety of potential functions, has the ability to stimulate proliferation and differentiation in osteoblasts in vitro [4]. Prompting of the differentiation process by treatment with zeolite would therefore enhance bone formation. Although differentiation is essential to cell function, manipulation of the process, or the dedifferentiation of osteoblasts would allow for a possible mechanism for regeneration of bone tissue by returning cells to their proliferative state. Dedifferentiation is defined as a cellular process in which a partially or completely differentiated cell reverts to an earlier developmental stage. This progression is often found in basal life forms and plants as a method of regeneration. Mammals have very limited ability to regenerate bone, however, other vertebrates, such as zebrafish, have the ability to entirely restore amputated bony structures through dedifferentiation of mature osteoblasts [4]. Since osteoblast dedifferentiation has the ability to allow for regeneration of bone in zebrafish, it is conceivable that manipulation of the osteoblast differentiation process, via treatment of osteoblasts with zeolite, could have implications for human bone repair. The purpose of this in vitro experiment was to determine the effect of the chelator, zeolite, on osteoblasts with regard to differentiation and analyze the significance of this research for the treatment of osteoporosis by means of osteogenesis and regeneration of bone tissue.