Type 1 diabetes mellitus induced low bone turnover in ovariectomized rats
Bo Liu1,2* Wei Feng2,3*, Tomoka Hasegawa4, Norio Amizuka4 and Minqi Li2
1Department of Stomatology, Jining Medical University, 2Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, 3Department of Endodontics, Jinan Stomatological Hospital, Jinan, China and 4Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan
*Bo Liu and Wei Feng have equaly contributed to this article
Offprint requests to: Minqi Li, Department of Bone Metabolism, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Wenhua West Road 44-1, Jinan 25012, China. e-mail: liminqi@sdu.edu.cn
Summary. To investigate type 1 diabetes mellitus (T1DM) affecting bone remodeling in the context of menopause in female rats. The animals were subjected to either ovariectomy (OVX) which was performed to mimic postmenopausal estrogen deficiency, and/or type 1 diabetes mellitus which was established by the intra-abdominal administration of 50 mg/kg streptozotocin (STZ). Single-loaded groups were the OVX group and the STZ group, while the combined group was the OVX+STZ group. Bone histomorphometry was performed on the tibial metaphysis by Micro-CT scanning. Immunohistochemistry was used to assess the activity of osteoblast and osteoclast by counteracting with antibodies against their respective specific marker enzymes. The gene expression of key molecules involved in osteoblastic and osteoclastic signaling pathways were analyzed by RT-qPCR. The results showed a significant bone volume decrease in both single-loaded groups and combined group with the combined group suffering greatest bone loss and bone structural deterioration (p<0.001). Immunohistochemical staining and RT-qPCR revealed an increase in osteoblastic (p<0.001) and osteoclastic (p<0.01) activities in OVX rats while there was a decrease (p<0.05) in those of STZ rats. When OVX and STZ were combined, the rats exhibited a further decrease in osteoblastic activity (p<0.001) and a similar level of osteoclastic activity (p>0.05) compared to their STZ counterparts. These results demonstrated that STZ-induced T1DM reverses OVX-associated high bone turnover osteoporosis to the type of low bone turnover, leading to greater bone loss and structural defect. Histol Histopathol 34, 57-67 (2019)
Key words: Type 1 diabetes mellitus, Ovariectomy, Bone turnover, Osteoporosis
DOI: 10.14670/HH-18-024