Diverse mechanisms of KLFs in skeletal diseases and their clinical potentials.

Krüppel-like factors (KLFs) constitute a family of zinc finger DNA-binding proteins that are critical regulators of skeletal development and pathogenesis. Through their highly conserved zinc finger domains, KLFs modulate a diverse array of cellular activities, including proliferation, differentiation, apoptosis, and autophagy, by regulating the transcription of target genes. A growing body of evidence has revealed aberrant expression of KLFs in a spectrum of skeletal disorders, significantly advancing our understanding of their roles in conditions such as osteoporosis, impaired fracture healing, osteoarthritis (OA), and bone tumors. Consequently, KLFs have emerged as promising biomarkers for early-phase diagnosis and viable targets for novel therapeutic strategies, highlighting their potential in the advancing field of precision medicine for skeletal diseases. This review synthesizes current knowledge on the regulatory mechanisms of KLFs across major skeletal pathologies, with a particular focus on their functions in osteoblasts, osteoclasts, and chondrocytes. Furthermore, it explores the clinical potential of KLFs as diagnostic biomarkers and therapeutic targets for drug development. A deeper understanding of the precise molecular mechanisms governing KLF activity is essential to translate this knowledge into novel diagnostic and therapeutic modalities for skeletal diseases.