Erratum: Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis: Erratum.

[This corrects the article DOI: 10.7150/thno.17949.].

Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis.

Rationale: The impaired function of endogenous bone marrow mesenchymal stem cells (BMMSCs) is a determinant in the development of osteoporosis (OP). Recent researches have proved that autophagy plays an important role in maintenance of skeletal phenotype. However, whether autophagy affects the development of OP through regulating the function of BMMSCs remains elusive. Methods: Ovariectomy (OVX)-induced OP model and sham model were established in 8-week-old C57 mice. The differentiation and immunoregulation properties of BMMSCs from two models were examined by osteogenic/adipogenic induction in vitro and treatment of a dextran sulfate sodium (DSS)-induced mice colitis model in vivo. We evaluated autophagy activity in sham and OVX BMMSCs by quantitative real time-polymerase chain reaction (qRT-PCR), western blotting, laser confocal microscopy and transmission electron microscopy (TEM). Finally, to testify the effects of rapamycin, short hairpin RNA (shRNA) -BECN1 (shBECN1) and shRNA-ATG5 (shATG5), we performed Alizarin Red staining and Oil Red O staining to detect lineage differentiations of BMMSCs, and carried out micro-CT, calcein staining and Oil Red O staining to assess the skeletal phenotype. Results: BMMSCs from OVX-induced OP model mice exhibited decreased osteogenic differentiation, increased adipogenic differentiation and impaired immunoregulatory capacity. Furthermore, autophagy decreased both in bone marrow and BMMSCs of osteoporotic mice. Importantly, regulation of autophagy directly affects the functions of BMMSCs, including differentiation and immunoregulatory capacities. Moreover, treatment with rapamycin rescued the function of endogenous BMMSCs and attenuated the osteoporotic phenotype in OVX mice. Conclusion: Our findings suggest that autophagy regulates the regenerative function of BMMSCs and controls the development of OP. The restoration of autophagy by rapamycin may provide an effective therapeutic method for osteoporosis.

Chitosan composite scaffold combined with bone marrow-derived mesenchymal stem cells for bone regeneration: in vitro and in vivo evaluation.

The study aimed to develop a chitosan (CS)-based scaffold for repairing calvarial bone defects. We fabricated composite scaffolds made of CS and bovine-derived xenograft (BDX), characterized their physicochemical properties including pore size and porosity, absorption, degradation, and compressive strength, compared their efficacy to support in vitro proliferation and differentiation of human jaw bone marrow-derived mesenchymal stem cells (hJBMMSCs), and evaluated their bone regeneration capacity in critical-size rat calvarial defects. The CS/BDX (mass ratio of 40:60) composite scaffold with porosity of 46.23% and pore size of 98.23 µm exhibited significantly enhanced compressive strength than the CS scaffold (59.33 ± 4.29 vs. 18.82 ± 2.49 Kpa). The CS/BDX (40:60) scaffold induced better cell attachment and promoted more osteogenic differentiation of hJBMMSCs than the CS scaffold. The CS/BDX (40:60) scaffold seeded with hJBMMSCs was the most effective in supporting new bone formation, as evidenced by better histomorphometry results, larger new bone area, and more obvious mature lamellar bone formation compared to other groups in rat calvarial defects 8 weeks after implantation. These results suggest that CS/BDX composite scaffold combining with hJBMMSCs has the potential for bone defect regeneration.