Early changes of bone metabolites and lymphocyte subsets may participate in osteoporosis onset: a preliminary study of a postmenopausal osteoporosis mouse model.

Purpose: Metabolic and immune changes in the early stages of osteoporosis are not well understood. This study aimed to explore the changes in bone metabolites and bone marrow lymphocyte subsets and their relationship during the osteoporosis onset. Methods: We established OVX and Sham mouse models. After 5, 15, and 40 days, five mice in each group were sacrificed. Humeri were analyzed by microCT. The bone marrow cells of the left femur and tibia were collected for flow cytometry analysis. The right femur and tibia were analyzed by LC-MS/MS for metabolomics analysis. Results: Bone microarchitecture was significantly deteriorated 15 days after OVX surgery. Analysis of bone metabolomics showed that obvious metabolite changes had happened since 5 days after surgery. Lipid metabolism was significant at the early stage of the osteoporosis. The proportion of immature B cells was increased, whereas the proportion of mature B cells was decreased in the OVX group. Metabolites were significantly correlated with the proportion of lymphocyte subsets at the early stage of the osteoporosis. Conclusion: Lipid metabolism was significant at the early stage of the osteoporosis. Bone metabolites may influence bone formation by interfering with bone marrow lymphocyte subsets.

Bone marrow fatty acids affect osteoblastic differentiation through miR-92b-3p in the early stages of postmenopausal osteoporosis.

Osteoporosis is partially caused by dysfunctions in the commitment, differentiation or survival of osteoblasts. Bone marrow fatty acids affect bone resorption and formation. In this study, we aimed to explore the role of fatty acids in the early stages of postmenopausal osteoporosis and determine whether they influence osteogenic differentiation through microRNAs. A quantitative analysis of bone marrow fatty acids early after ovariectomy or sham surgery in a rat osteoporotic model was performed using gas chromatography/mass spectrometry. The results showed that palmitoleate was significantly decreased on postoperative day 3 while both pentadecanoate and palmitoleate were significantly decreased on postoperative day 5 in rats in the ovariectomized group compared with those in the sham group. Palmitoleate promotes osteogenic differentiation, whereas pentadecanoate inhibits this process. Palmitoleate levels were higher than those of pentadecanoate; therefore, the early overall effect of significant bone marrow fatty acid changes was a decrease in osteogenic differentiation. We also found that miR-92b-3p inhibited osteoblastogenesis via the miR-92b-3p/phosphatase and tensin homolog regulatory axis. Palmitoleate, pentadecanoate, and palmitate influenced the osteoblastogenesis of MC3T3-E1 cells through miR-92b-3p. Taken together, we propose that miR-92b-3p mediates the effect of bone marrow fatty acids on osteoblast differentiation in the early stages of osteoporosis. These findings may provide molecular insights for the treatment of osteoporosis.

Changes in Bone Marrow Fatty Acids Early after Ovariectomy-Induced Osteoporosis in Rats and Potential Functions.

The aim of this study was to investigate the changes in bone marrow fatty acids early after ovariectomy-induced osteoporosis in rats, and explore the potential function of the bone marrow fatty acids. Ninety-six female Sprague Dawley rats (12 weeks) were randomly divided into an ovariectomized (OVX) group and Sham group (N = 48/group) and received ovariectomy or Sham surgery, respectively. After 3, 5, 7,14, 21 and 28 days, eight rats in each group were sacrificed to detect the composition of bone marrow fatty acids by means of gas chromatography-mass spectrometry and evaluate the trabecular bone microarchitecture by means of microCT. Bone marrow rinsing fluid and serum were collected for the detection of nitric oxide synthase/nitric oxide (NOS/NO) and bone metabolism related parameters, respectively. Our results demonstrated that the bone microstructure was damaged significantly from 14 days after OVX surgery onwards. Sample clustering and group separation were observed between the OVX group and Sham group 3 and 14 days after surgery, which suggested the role of bone marrow fatty acids in the early stage of postmenopausal osteoporosis. Palmitoleate, myristate and arachidonate were found to play an important role in classification between the OVX group and Sham group on the 3rd day after surgery (VIP > 1, p < 0.05). Palmitoleate, myristate, alpha linolenate, stearate and eicosenoate were found to play an important role in classification between the OVX group and Sham group on the 14th day after surgery (VIP > 1, p < 0.05). The levels of myristate, palmitoleate, alpha linolenate and eicosenoate were significantly decreased in the OVX group, while the levels of arachidonate and stearate were significantly increased in OVX group (p < 0.05). Additionally, myristate, palmitoleate, alpha linoleate and eicosenoate were negatively correlated with C-terminal telopeptide of type 1 collagen (CTX-1, a bone resorption marker), while arachidonate was negative correlated with osteocalcin (OCN, a bone formation marker) (p < 0.05). A significant correlation was also found between eicosenoate and NOS (p < 0.05). Profound bone marrow fatty acids changes have taken place in the early stage of post-menopausal osteoporosis. They may affect bone formation though affecting the differentiation and function of osteoclasts or osteoblasts, respectively. The NOS/NO system may mediate the influence of eicosenoate on bone formation.

Bone microarchitectural parameters can detect oxytocin induced changes prior to bone density on mitigating bone deterioration in rabbit osteoporosis model using micro-CT.

BACKGROUND: This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. METHODS: Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. RESULTS: Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. CONCLUSION: BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.