Preclinical study identifies targets against osteoporosis and bone metastasis

Osteoclast cells are responsible for the resorption of bone structure and minerals, and their dysregulation is associated with osteoporosis, or decreased bone mineral density. Building upon previous work showing that MALAT1, a long noncoding RNA (lncRNA), suppresses breast cancer metastasis, Li Ma, Ph.D., and colleagues noted that a specific mutation in MALAT1 was associated with low bone mineral density and sought to determine the role of MALAT1 alternations in bone diseases. MALAT1 deficiency led to osteoporosis and more severe bone metastases of melanoma and mammary tumor cells in lab models, but was reversed when MALAT1 was re-introduced. Single-cell analysis of bone samples from patients showed that reduced MALAT1 expression in pre-osteoclasts and osteoclasts was associated with osteoporosis and metastatic bone lesions. The researchers discovered that MALAT1 suppresses osteoclast differentiation and protects against metastasis by binding and inhibiting a specific target, TEAD3, suggesting TEAD inhibitors could make up for the reduction of MALAT1. The study reveals the fundamental roles of MALAT1 lncRNA in physiological and pathological processes and identifies TEAD inhibitors as a potential approach to treat osteoporosis and bone metastasis.