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A new role for the A2b adenosine receptor in mesenchymal stem cell differentiation and bone fracture healing
Author(s) -
Carroll Shan H,
Wigner Nathan A,
JohnstonCox Hillary,
Kulkarni Nitin,
Gerstenfeld Louis C,
Ravid Katya
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.679.1
The A2b adenosine receptor (A2bAR) has a protective role in various models of chronic injury and in inflammation. Bone fracture healing is a complex process composed of an initial inflammatory response followed by the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and osteoblasts to form bone and finally resorption by osteoclasts to remodel the structure. A2bAR KO mice display delayed fracture healing with lower expression of osteoblast differentiation genes and dysregulated expression of chondrocyte markers. Furthermore, micro‐CT analysis of adult femurs shows lower bone density in A2bAR KO mice. In vitro, induced differentiation of bone marrow derived MSCs from A2bAR KO mice resulted in lower expression of osteoblast differentiation transcription factors, including Msx1 and osterix, and formed fewer mineralized nodules, as compared to wildtype mice. Additionally, concurrent treatment of bone marrow derived MSCs with A2bAR agonists during differentiation resulted in elevated expression of Msx1 and osterix. These result demonstrate a role for the A2bAR in MSC differentiation and in bone formation and healing.