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A requirement for STAT3 in limb development
Author(s) -
Rigueur Diana,
Lopez Noah,
Lyons Karen
Publication year - 2021
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.2021.35.s1.04614
Subject(s) - cartilage , stat3 , microbiology and biotechnology , osteoarthritis , effector , phenotype , zebrafish , signal transduction , mesenchyme , biology , medicine , anatomy , pathology , embryo , genetics , gene , alternative medicine
The Interleukin‐6/STAT3 (IL‐6/STAT3) signaling pathway is essential for proper immune response to invading pathogens and viral infections. Moreover, STAT3 has high implications as a therapeutic target for rheumatoid and osteoarthritis. Recent literature has found that the IL‐6/STAT3 signaling pathway plays an imperative role in the development of cartilage and bone. However, the direct role and the downstream effectors of STAT3 signaling during cartilage formation remains elusive. Through the use of cleared skeletal preparations, and histology, conditional loss of STAT3 in mouse cartilage, via the Col2‐Cre driver, show that STAT3 is essential for proper limb growth plate formation. Furthermore, loss of STAT3 results in spontaneous bone fractures of the humerus. Interestingly, these severe fractures are rapidly repaired, underscoring an untapped mechanism for regeneration in musculoskeletal tissue. Moreover, conditional loss of STAT3 in limb mesenchyme, via the Prx1‐Cre driver was generated. Loss of STAT3 in mesoderm show contortion phenotypes in the humerus. The stronger limb phenotype of Prx1Cre;Stat3 fxfx compared to Col2Cre;Stat3 fxfx mice indicates that Stat3 may exert effects at multiple stages of endochondral bone formation. Future experiments elucidating the downstream effectors of STAT3 mediated pathways will reveal the mechanisms by which STAT3 modulates different processes in limb development.