Patients with
diabetes mellitus are known to develop
osteopenia and
osteoporosis, apparently as a reduction in the process of bone formation. In order to evaluate whether bone-modulating
hormones--
estradiol,
testosterone, and 1,25(OH)(2)D(3)--have different effects on osteoblasts derived from diabetic and from normal non-diabetic rats, we studied the specific effects of these
hormones on the differentiation and function of cultured osteoblasts derived from 1-year-old Cohen diabetic rats. (The Cohen diabetic model consists of a diabetic-sensitive strain [CDs; diabetic] and a diabetic-resistant strain [CDr; normal]). The CDs and CDr male and female rats were fed on a regular diet (RD) or a high-
sucrose low-
copper diet (HSD; diabetogenic). On the HSD diet, only CD rats develop
type 2 diabetes, while CDr do not. Bones were removed for primary osteoblast cultures, and osteoblastic responses to the bone-modulation
hormones--
estradiol,
testosterone, and 1,25(OH)(2)D(3)--were studied. In male rats fed RD, primary cultures of osteoblasts without
hormone addition to the culture medium showed that
alkaline phosphatase (ALP) activity was similar in the Cohen diabetic rats (both CDr and CDs) to that of the original Sabra strain. However,
collagen synthesis was reduced in the CDr and CDs compared to the Sabra strain. The addition of the
hormones to the culture medium did not change ALP activity or
collagen synthesis in the male-derived osteoblasts, but increased mineralization in all strains. In female rats (studied only in CDs and CDr animals) there were no differences between animals fed the RD. HSD increased the basal activity of ALP in the CDr but not in the CDs rats, and decreased the rate of
collagen synthesis in both CDr and CDs (diabetic) animals. The addition of the bone-modulation
hormones to the culture medium further increased ALP activity in the osteoblasts derived from the CDr animals, while decreasing ALP activity in the CDs. These
hormones also decreased
collagen synthesis in both strains and increased mineralization in all osteoblasts. In conclusion, the metabolic status (HSD and diabetes) in rats prior to culture affected the phenotype of cultured osteoblasts, decreasing their response to bone-modulation
hormones. This decreased response, especially to
estradiol, may be a major cause of the
osteopenia observed in diabetes.