Malat1, a highly conserved long noncoding RNA (lncRNA), is abundantly expressed in normal tissues and has been shown to suppress breast cancer lung metastasis. This study reveals that Malat1 protects against osteoporosis and bone metastasis by inhibiting osteoclastogenesis. Malat1 is downregulated during osteoclast differentiation in humans and mice, and its deficiency promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic restoration of Malat1. Mechanistically, Malat1 binds to Tead3, a macrophage-osteoclast-specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis. This results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. These findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis. Osteoporosis is characterized by decreased bone mineral density, increased bone fragility, and susceptibility to fracture, and is associated with excessive osteoclastogenesis. Osteoclasts, multinucleated giant cells derived from the monocyte/macrophage lineage, are responsible for bone resorption. The nuclear factor of activated T cells 1 (NFATC1) is a master regulator of osteoclastogenesis, and Malat1 inhibits NFATC1 activity by sequestering Tead3. Malat1 deficiency promotes osteoclastogenesis through the activation of Nfatc1. Malat1 overexpression in RAW264.7 cells and U937 cells inhibits osteoclastogenesis. Malat1 binds to Tead3 to inhibit Nfatc1 activity and osteoclastogenesis. These findings suggest that Malat1 functions as a suppressor of both mouse and human osteoclastogenesis. The study highlights the role of Malat1 in regulating osteoclastogenesis and bone homeostasis, and its potential as a therapeutic target for osteoporosis and bone metastasis.Malat1, a highly conserved long noncoding RNA (lncRNA), is abundantly expressed in normal tissues and has been shown to suppress breast cancer lung metastasis. This study reveals that Malat1 protects against osteoporosis and bone metastasis by inhibiting osteoclastogenesis. Malat1 is downregulated during osteoclast differentiation in humans and mice, and its deficiency promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic restoration of Malat1. Mechanistically, Malat1 binds to Tead3, a macrophage-osteoclast-specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis. This results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. These findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis. Osteoporosis is characterized by decreased bone mineral density, increased bone fragility, and susceptibility to fracture, and is associated with excessive osteoclastogenesis. Osteoclasts, multinucleated giant cells derived from the monocyte/macrophage lineage, are responsible for bone resorption. The nuclear factor of activated T cells 1 (NFATC1) is a master regulator of osteoclastogenesis, and Malat1 inhibits NFATC1 activity by sequestering Tead3. Malat1 deficiency promotes osteoclastogenesis through the activation of Nfatc1. Malat1 overexpression in RAW264.7 cells and U937 cells inhibits osteoclastogenesis. Malat1 binds to Tead3 to inhibit Nfatc1 activity and osteoclastogenesis. These findings suggest that Malat1 functions as a suppressor of both mouse and human osteoclastogenesis. The study highlights the role of Malat1 in regulating osteoclastogenesis and bone homeostasis, and its potential as a therapeutic target for osteoporosis and bone metastasis.