STAT3 is essential for proper limb skeletal development

Abstract

The Interleukin‐6/STAT3 (IL‐6/STAT3) signaling pathway has been well investigated in the development of the immune system and in disease. From autoimmune disorders, cancers, rheumatoid, and osteoarthritis, STAT3 gain‐of‐function and loss‐of‐function studies have shown that in humans, its regulation is imperative for control of disease. However, the precise role that STAT3 and its downstream effectors play in the formation, maintenance, and disease of the skeleton, remain understudied. Our recent work shows that STAT3 is imperative for multiple aspects of limb skeletal development. Through whole‐mount skeletal preparations, X‐ray micrographs, and histology, conditional loss of STAT3 in limb, via the Prx1‐Cre driver, show that STAT3 mediates proper cartilage, bone, tendon, and ligament formation. Moreover, loss of STAT3 results in severe bending and twisting of the fore and hind limbs, as well as abnormal tendon and ligament attachments. Furthermore, loss of STAT3 shows forelimb regional specificity of ectopic bone formation. Additional investigation of STAT3 mediated downstream effectors can identify a mechanism involved in proper cartilage and bone formation, as well as tendon and ligament‐to‐bone integration. Fundamental understanding of the role STAT3‐mediated signaling plays in skeletal formation may identify future therapeutics for regenerative medicine in tendon/ligament bone repair.Support or Funding InformationNIH R01 80094