A healthy skeleton is crucial for a child’s ability to grow and develop without experiencing pain or fractures. However, skeletal dysplasias and disorders of bone mineralization disrupt healthy bone accrual in childhood, leading to chronic pain, joint problems, and even threatening the function of a child’s vital organs. Disorders of the skeleton arise from abnormalities in the growth and mineralization of bone. During healthy bone growth, stem cells in the growth plate transform into chondrocytes, the cells that make cartilage. These chondrocytes then multiply and mature, while forming a cartilage scaffold that is eventually mineralized to bone by the bone-building cells, osteoblasts. Recent research has unveiled that some mature chondrocytes have the remarkable capability to transform into osteoblasts, yet, how cells actually transform remains poorly understood. A better understanding of this process will allow doctors and scientists to develop targeted therapies for diseases of skeletal malformation and under-mineralization of bone.

Our investigations focus on a gene called “PIAS1” that we have found is involved in the maturation of chondrocytes. We hypothesize that PIAS1 may be involved in progression of chondrocytes to osteoblasts. To delve deeper into this phenomenon, we will conduct experiments both in three-dimensional cultures of chondrocytes and with mice to investigate how manipulating PIAS1 affects the transformation of chondrocytes into osteoblasts. Understanding the role of PIAS1 in this process holds promise for developing novel treatments for skeletal dysplasias and bone disorders in children. By enhancing the transformation of cartilage cells into bone cells, we may pave the way for therapies that promote stronger, healthier bones in children with skeletal disease, enabling them to lead more active, pain-free lives.