gms | German Medical Science

Objectives: Osteocytes act as mechanosensors to control bone volume. However, the specific role of osteocytes in regulating bone homeostasis in diseased bone is not well understood. Osteocytes role in fat cell metabolism also remains unclear. The current study aims is to correlate osteocyte morphology and adipocytes accumulation in bone marrow with the progression of osteoporosis in sheep model.

Methods: Thirty-one female merino-land sheep (5.5 years age) were randomly divided into: Control, Ovariectomy (OVX), OVX with dietary deficiency (OVXD), and OVXD with steroid injection (OVXDS). The animals were euthanized after (month=M) 0M, 3M, and 8M. Radiological testing using Dual-energy X-ray absorptiometry DXA, serum analysis, molecular analysis, and histological analysis were carried out. The direct influence of osteocytes on adipocyte transition was examined through immunostaining of BMP7, UCP1, PGC1 alpha, and PRDM16 with silver nitrate as counter staining.

Results and conclusion: DXA revealed an increase of body fat in OVXDS (p-value ≤0.05 between the time points) and negatively correlated with Bone Mineral Density (BMD) with treatment progression. Significant decrease in BMD was seen in OVXDS at 3M and 8M (p-value ≤0.05, and 0.026, respectively). ECM degradation and trabecular thinning in OVXDS hallmarked osteoporotic bone status. Count of empty lacunae and adipocytes increased when treatment severity and duration increased. Immunostaining BMP7, UCP1, PGC1 alpha, and revealed a positive signal in spherical shaped osteocytes. Interestingly, PRDM16 signal location shifted from only in adipocytes at 0M, to adipocytes and osteocytes at 3M to mainly in osteocytes at 8M.

OVX in combination with multi-deficient diet and steroid administration showed the osteoporotic bone status after 8M. Fat cells markers signals were located within osteocyte vicinity after 8M, thereby indicating a regulatory mechanism. To our knowledge, our study for the first time showed the frequent presence of fat cells markers within spherical shaped osteocytes rather than spindle shaped osteocytes. The results draw a direct relation between bone marrow fat and osteocytes. Further small animal models of osteoporosis are being investigated to get a deeper insight through more detailed treatment. Understanding the role of osteocytes in regulating fat metabolism might suggest cell specific therapeutic targeting to prevent osteoporotic fractures.