Semaphorin 3A promotes osteogenic differentiation of BMSC from type 2 diabetes mellitus rats
- 118 Downloads
Bone regeneration is impaired in patients with type 2 diabetes mellitus (T2DM), which leads to non-healing after bone loss. The decreased osteogenic capacity of bone mesenchymal stem cells (BMSCs) might be a main reason. Sema3A, as a powerful protein promoting osteocyte differentiation, shows potential for bone regeneration treatment. BMSCs may be a therapeutic solution. In this study, we divided BMSCs from T2DM rats (BMSCs-D) and normal rats (BMSCs-N), identified their ability to differentiate into different cell types. Then we found decreased expression of Sema3A in BMSCs-D compared with BMSCs-N. Stimulating with Sema3A showed no influence in the proliferation or migration of BMSCs. However, Sema3A stimulation significantly increased the expression of osteogenic‑related genes, including type I collagen, alkaline phosphatase, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein and osteocalcin. Besides, the osteogenic capacity of BMSCs was also increased by Sema3A stimulation. In conclusion, we proved that exogenous Sema3A stimulation might repair the osteogenic capacity of BMSCs-D, thus providing a new strategy for restoring the impaired bone regeneration ability for T2DM patients.
KeywordsSemaphorin-3A Diabetes mellitus, Type 2 Bone mesenchymal stem cells Bone regeneration
This study is supported by the National Natural Science Foundation of China [NO. 81470775]. Department of Burns and Cutaneous Surgery provided most of the equipment of experiment.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Fang K, Song W, Wang L, Jia S, Wei H, Ren S, Xu X, Song Y (2014) Immobilization of chitosan film containing semaphorin 3A onto a microarc oxidized titanium implant surface via silane reaction to improve MG63 osteogenic differentiation. Int J Nanomed 9:4649–4657Google Scholar
- Hamann C, Goettsch C, Mettelsiefen J, Henkenjohann V, Rauner M, Hempel U, Bernhardt R, Fratzl-Zelman N, Roschger P, Rammelt S et al (2011) Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Endocrinol Metab 301:E1220-E1228CrossRefGoogle Scholar
- Lapmanee S, Charoenphandhu N, Aeimlapa R, Suntornsaratoon P, Wongdee K, Tiyasatkulkovit W, Kengkoom K, Chaimongkolnukul K, Seriwatanachai D, Krishnamra N (2014) High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats. Lipids 49:975–986CrossRefPubMedGoogle Scholar
- Liu Y, Yang X, Maureira P, Falanga A, Marie V, Gauchotte G, Poussier S, Groubatch F, Marie PY, Tran N (2017) Permanently hypoxic cell culture yields rat bone marrow mesenchymal cells with higher therapeutic potential in the treatment of chronic myocardial infarction. Cell Physiol Biochem 44:1064–1077CrossRefPubMedGoogle Scholar
- Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT, Pearce S, Kasten P (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31:3572–3579CrossRefPubMedGoogle Scholar
- Oei L, Zillikens MC, Dehghan A, Buitendijk GH, Castano-Betancourt MC, Estrada K, Stolk L, Oei EH, van Meurs JB, Janssen JA et al (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study. Diabet Care 36:1619–1628CrossRefGoogle Scholar