Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 18, Issue 2, Pages 572-584Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.63505
Keywords
Irisin; mesenchymal stem/stromal cell; Osteogenesis; BMP/SMAD signaling; alpha V integrin
Categories
Funding
- Wuxi Top medical expert team of Taihu Talent Program
- National Natural Science Foundation of China [81972059, 81772313]
- Social Development Project of Jiangsu Province [BK2019668]
- Natural Science Foundation of Jiangsu Province General Project [BK20181130]
- Priority Academic Program Development of Jiangsu Higher EducationInstitutions (PAPD)
Ask authors/readers for more resources
Irisin plays a regulatory role in bone homeostasis and promotes MSC-derived osteogenesis. Lack of Irisin leads to bone loss and enhanced bone resorption, while the presence of Irisin can promote osteogenesis by activating signaling pathways.
Irisin is well-known to contribute to bone homeostasis due to its bidirectional regulation on osteogenesis and osteoclastogenesis. However, the mechanisms of irisin involved in mesenchymal stem/stromal cells (MSCs)-derived osteogenesis are still under investigated. Fibronectin type III domain-containing protein 5 (FNDC5) is the precursor protein of irisin, compare with wild type (WT) littermates, FNDC5-/- mice lost bone mass significantly, collectively evidenced by the decrease of bone mineral density (BMD), impaired bone formation and reduced N-terminal propertied of type I procollagen (P1NP) in sera. Meanwhile, the bone resorbing of FNDC5-/- mice has enhanced accompanied by increased tartrate phosphatase (TRAP) staining cells morphologically and cross-Linked C-telopeptide of type 1 collagen (CTX) level in sera. In vitro study showed that lack of irisin impeded the MSC-derived osteogenesis of FNDC5-/- mice. The addition of irisin promote the osteogenesis of WT and irisin-deficient MSCs, by activating alpha V integrin-induced ERK/STAT pathway, subsequently enhancing bone morphogenetic protein 2 (BMP2) expression and BMP/SMAD signaling activation. Taken together, these findings further indicate that irisin regulates bone homeostasis. Moreover, irisin promotes MSC-derived osteogenesis by binding to alpha V integrin and activating BMP/SMAD signaling consequently. Thus, irisin may be a promising therapeutic target for osteoporosis and bone defects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available