Molecular mechanisms of long bone growth and chondrocyte regulation: A narrative review

Long bone growth is a fundamental determinant of final height. Growth, metabolism, and differentiation of chondrocytes, which are the key cellular players in this process, are regulated by systemic hormones, local factors, and cellular signaling pathways. This review provides an overview of the structural aspects of the growth plate, factors influencing chondrocyte function, and their impact on longitudinal bone growth. Systemic factors, including growth hormone, sex hormones, thyroid hormone, glucocorticoids, leptin, and insulin significantly affect chondrocyte proliferation and hypertrophy. Local factors, including transcription factors such as SRY-box 9 protein (SOX9), Runt-related transcription factor 2 (RUNX2), and bone morphogenetic proteins (BMPs), along with signaling pathways such as the Wnt pathway, play critical roles in chondrocyte proliferation and differentiation. These factors regulate gene expression, cell differentiation, and extracellular matrix synthesis. Additionally, Indian hedgehog (Ihh) and C-type natriuretic peptide (CNP) are involved in the complex signaling network governing chondrocyte function. Understanding molecular mechanisms underlying normal growth plate function has provided valuable insights into the genetic defects that impact growth and foundation for the development of effective therapeutic strategies for individuals with growth disorders.