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Hard tissue formation, also known as biomineralization, is the physiological process by which living organisms produce mineralized tissues such as bone, dentin, and tooth enamel [1, 13]. This process involves the orchestration of specialized cells—including osteoblasts, odontoblasts, and ameloblasts—that secrete an organic extracellular matrix which subsequently undergoes controlled mineral deposition, primarily in the form of hydroxyapatite crystals [1, 8]. While not a single molecular target, hard tissue formation represents a critical therapeutic endpoint in regenerative medicine and metabolic bone disease. Drugs like bisphosphonates and RANKL inhibitors (e.g., denosumab) are used to manage the rate of bone resorption, effectively preserving hard tissue, while anabolic agents like teriparatide and sclerostin inhibitors (e.g., romosozumab) promote the formation of new mineralized tissue [2, 11]. In surgical applications, bone morphogenetic proteins (specifically BMP-2) are utilized to induce de novo hard tissue formation for spinal fusion and fracture repair [10, 14]. Disruptions in this process are central to the pathogenesis of conditions such as osteoporosis, osteogenesis imperfecta, and various dental mineralization defects [8, 15].
Therapeutic agents modulate hard tissue formation by either inhibiting osteoclast-mediated mineral resorption or by stimulating the differentiation and secretory activity of osteoblasts and odontoblasts through signaling pathways such as Wnt/β-catenin and BMP/TGF-β.
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