gms | German Medical Science

Objective: Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content.

Here we hypothesized that bilateral ovariectomy and dietary limitation in a rat model of osteoporosis show the correlation between extracellular matrix (ECM) proteins regulation and osteocyte localization, activity and networks.

Method: Female Sprague-Dawley rats 14 weeks of age were randomly divided into 2 groups: (i) Sham-operated group (Sham, 12M, and 14M, n=8/ time-point); (ii) ovariectomized + multi-deficient diet (OVX+Diet, 12M, and 14M, n=8 / time-point), which was supplemented with deficient diet. Osteocyte morphology and networks were detected using silver and rhodamine staining. ECM proteins were investigated through immunohistochemistry. Cellular populations were tested using enzymehistochemistry. Mineralization of osteocytes and purlieus took place using time of flight secondary ion mass spectrometry (TOF-SIMS). Statistical analysis was performed using Mann Whitney U test with Bonferroni correction.

Results and conclusion: In the OVX+Diet L2 vertebra and compared to the controls regions, were osteocytes function is compromised, local osteomalatic lesions characterized by the presence of excessive unmineralized osteoid were seen. Nonetheless, ECM proteins indicating high bone turnover (osteocalcin, biglycan) were noticed to increase within these regions and were accompanied by the presence of apoptotic osteocytes. On the other hand, the presence of cell adhesive and anchorage molecules (fibronectin, and tenascinc) that interact with integrin beta 5 was deteriorated, indicating that changes in ECM architecture resulted from tainted mechanical response. Furthermore, indications of osteoporotic bone status was implied by 1) higher positive area of tartrate resistant acid phosphatase staining (TRAP), 2) stronger signals of matrix metalloproteinase (MMP-9), 3), which altogether suggest a higher osteoclast-mediated resorption as typically seen in osteoporotic patients.

The described three cell types are the key players to bone metabolism through production and mineralization of ECM or resorption. The current study indicates the importance in therapeutically targeting osteocytes to regulate bone metabolism in osteoporotic /osteomalatic bone. Recently, osteoblast proliferation via integrin signals in the ECM was correlated with the activation of ERK. Such novel finding was also seen in this study and could provide an understanding of the cellular imbalance reported in this study especially that therapeutically targeting of ERK.