Effect of zoledronic acid on jaw bone marrow mesenchymal stem cells in mice with bisphosphonate-related osteonecrosis of the jaw

doi:10.12307/2026.308

Abstract

Abstract: BACKGROUND: Bisphosphonates, as the core drugs of anti-bone resorption therapy, are widely used in the treatment of metabolic bone diseases. However, long-term use can cause the complications of bisphosphonate related osteonecrosis of the jaw. The traditional pathogenesis focuses on the inhibitory effect of bisphosphonates on osteoclasts, but it is difficult to fully explain the pathological development of osteonecrosis. Compared with the relatively mature osteoclast research, there are fewer reports on the effects of bisphosphonates on the biological characteristics and functions of osteoblast-related cells, and there are differences between some reports. This difference may be due to the experimental system, drug concentration and cell source, highlighting the necessity of conducting systematic and standardized research.
OBJECTIVE: To investigate the effect of the third-generation bisphosphonate-zoledronic acid commonly used in clinical practice on the healing of tooth extraction sockets and the proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells derived from the jaw in mice.
METHODS: Sixteen C57B/6J male mice were randomly divided into control group and experimental group. The experimental group was intraperitoneally injected with zoledronic acid combined with subcutaneous injection of dexamethasone; the control group was injected with the same amount of PBS. The left maxillary first molars of all mice were extracted after 2 weeks of injection, and the samples were sacrificed after 2 weeks of injection. The bone reconstruction and mucosal healing of the tooth extraction socket were observed by general observation of the wound of the tooth extraction socket, Micro CT imaging and three-dimensional reconstruction analysis, and hematoxylin-eosin staining. Bone marrow mesenchymal stem cells derived from the mandibular bones of the two groups of mice were isolated and cultured. After normal culture and osteogenic induction culture, the effects of zoledronic acid on cell proliferation, migration and osteogenic differentiation were observed by CCK-8 assay, qPCR, western blot assay, alkaline phosphatase staining, and Alizarin red staining.
RESULTS AND CONCLUSION: (1) Compared with the control group, the bone and mucosa of the tooth extraction socket in the experimental group were poorly healed, and the inflammatory cell infiltration was more obvious. (2) Compared with the control group, the proliferation and migration abilities of bone marrow mesenchymal stem cells derived from the jaw in the experimental group were significantly inhibited (P < 0.05). (3) Compared with the control group, the alkaline phosphatase staining of bone marrow mesenchymal stem cells derived from the jaw in the experimental group was weaker, the number of calcium nodules decreased, and the expressions of alkaline phosphatase, bone sialic protein 2, type I collagen α1 chain and Runt-related transcription factor 2 were decreased (P < 0.05). The results showed that zoledronic acid could adversely affect the healing of the tooth extraction socket in mice, which may be related to the inhibition of the proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells derived from the jaw.

Key words: bisphosphonate, osteonecrosis of the jaw, zoledronic acid, jaw, tooth extraction socket, mesenchymal stem cell, proliferation, migration, osteogenic differentiation

CLC Number:

Li Pengli, Yang Yanmei, Hu Yawen, Liu Hongqi, Wang Manyi, Yan Jianfei, Gu Bin. Effect of zoledronic acid on jaw bone marrow mesenchymal stem cells in mice with bisphosphonate-related osteonecrosis of the jaw[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(13): 3217-3225.

Figures/Tables 4

References

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