Prevention of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells

Abstract

The SAMP6 mouse spontaneously develops osteoporosis early in life and is therefore a useful model for examining the mechanisms underlying osteoporosis. We have recently established a new bone marrow transplantation (BMT) method: the bone marrow cells (BMCs) of normal allogeneic mice are directly injected into the bone marrow cavity of irradiated recipients (IBM-BMT). Using IBM-BMT, we attempted to prevent osteoporosis in SAMP6 mice. The hematolymphoid system was completely reconstituted with donor-type cells after IBM-BMT. Thus-treated SAMP6 mice showed marked increases in trabecular bone even at 12 months of age, and the bone mineral density (BMD) remained similar to that of normal B6 mice. Urinary deoxypiridinoline (DPD) also remained continuously low until 10 months of age. In addition, bone marrow stromal cells in the treated SAMP6 mice were replaced by donor stromal cells. The message levels of both IL-11 (known as an important factor of bone remodeling) and IL-6 (known to enhance osteoclastogenesis) were restored to normal. These results indicate that the bone marrow microenvironment is normalized after IBM-BMT, and that the increased production of IL-11 and IL-6 ameliorates the imbalance between bone absorption and formation, resulting in the prevention of osteoporosis in SAMP6 mice.