JAK-STAT and bone metabolism

Abstract

Emerging evidences suggest Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway plays an important role in bone development and metabolism. Effects of JAK-STAT pathway on skeletal development are summarized based on skeletal phenotype of individual JAK and STAT gene knockout mouse. Furthermore, STAT3 has more profound effects on bone homeostasis compared with the other STATs. STAT3 mutation causes a disease called Job syndrome, most patients with which have associated craniofacial and skeletal features. Selective inactivation of STAT3 in osteoblasts decreases bone formation and skeletal responsiveness to mechanical loading. Future research includes investigating JAK-STAT signaling in osteoclasts and osteocytes.

Keywords: Janus kinase; bone homeostasis; mechanotransduction; osteoblast; signal transducer and activator of transcription; skeletal development.

Figure 1. Kyphosis of a mouse with selective inactivation of STAT3 in osteoblasts/osteocytes occurs at the thoracic and lumbar regions in a radiograph (A). Histological examination at the spine (white square) shows deformity of vertebral bodies (B). Enlarged images of the histological section (yellow square) shows abnormally delayed endochondral ossicification as indication by the arrow (C). The histological section was stained with Von Kossa stain and bone tissues are stained black.

Figure 2. Scoliosis (A), minimal trauma pathological fracture at femur (B) and rickets (C) in HIES patients. Adapted from Primary Immunodeficiency Diseases: A Molecular and Cellular Approach, edited by Ochs, Smith and Puck. 2006.

Figure 3. Mechanical loading increase STAT3 expression in bone tissues. STAT3 positive osteoblasts at the periosteal surface of ulna and osteocytes in the cortex (indicated by arrows) were present in the loaded ulna (B) but not in the control ulna (A) by immunohistochemical staining with anti-STAT3 antibody, suggesting the involvement of STAT3 in mechanotransdcution.