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Wnt plays important roles in regulation of differentiation of osteoblast and chondrocyte and their function. Wnt family members ingeniously utilize canonical Wnt signaling pathway through β-catenin and non-canonical Wnt signaling pathway independent of β-catenin, consequently regulating development, formation and homeostasis of bone and cartilage. Recent studies revealed that canonical Wnt signal activates transcriptional regulator, TAZ, in addition to transcription factors, LEF and TCF. Canonical Wnt signal crosstalks with BMP signal by stimulating complex formation of LEF1, TAZ and Runx2. Although molecular mechanism of non-canonical Wnt signal is getting clearer, the precise role of non-canonical Wnt signal in bone and cartilage seems still elusive.

Chondrocytes, which are originated from undifferentiated mesenchymal stem cells, play roles in skeletal development and growth in mammal, and smooth movement of joints. Endochondral ossification is necessary for skeletal development, and the multiple and complex biological events are precisely regulated by several hormones, cytokines, and their downstream signaling and transcriptional regulation. On the other hands, articular chondrocytes physiologically retains their features during a lifetime. Numerous molecules involved in endochondral ossification have been identified and investigation of the molecular mechanisms have amazingly progressed. Although GDF5 and Prg4 were identified as important molecules associated with articular cartilage development and its homeostasis, the molecular mechanisms are very unclear to date.

Bone formation is the important factor which contributes to the successful periodontal tissue regeneration in periodontitis and osseointegration of implant placement. To achieve the sufficient bone volume in the process of dental treatment, several growth factors and hormones which enhance bone formation have been evaluated in clinical and preclinical studies. BMP2 and BMP7 have recently been approved for sinus augmentation by FDA. A phase2a randomized controlled clinical studies were conducted to evaluate the potential of GDF5 to stimulate periodontal tissue regeneration and GDF5 significantly stimulated alveolar bone regeneration compared to control. Moreover, increased alveolar bone formation was observed by the use of PTH (1-34) Teriparatide in patients of severe periodontitis. PTH and GDF5 are promising agents for future periodontitis treatment.

Bone is one of the most preferential metastatic target sites for cancers. The biological crosstalk between metastatic cancer cells and bone microenvironment is critical to the pathophysiology of bone metastases. For example, It is well established that PTH-rP production in cancer cells stimulated by bone-derived TGF-β facilitates bone metastasis through promoting bone resorption by osteoclasts, thereby establishing "vicious cycle" between metastatic cancer cells and bone. In addition, recent studies identified several new players including platelets and MDSCs which contribute to the development of bone metastasis. In this review, we will overview the current topics on the mechanism by which bone metastasis is modulated at cellular and molecular levels.

Chondrocytes are derived from mesenchymal stem cells and play an essential role in endochondral ossification. Transcription factors, Sox9, Runx2, Runx3 and Osterix are critical for endochondral ossification, and regulate differentiation of mesenchymal stem cells into chondrocytes, and proliferation, maturation and apoptosis of chondrocytes. Recent advances in gene cloning approaches utilizing microarray and high-throughput sequencing technologies have revealed functional regulatory mechanisms of these transcription factors and contributed to understanding of molecular mechanisms of complex and harmonious chondrocyte differentiation.

Genetic and biochemical studies have identified transcription factors critical and specific for bone and cartilage development. More recent studies revealed the molecular mechanisms how these transcription factors regulate bone and cartilage development. Especially, we appreciate recent advances in molecular function of the complex assembled by these transcription factors and epigenetic regulation of them. Aging, inflammation, biological stress, and disorder of endocrine system induce several bone and/or cartilage diseases by affecting the transcriptional and epigenetic regulation. In this review, we would like to describe the transcriptional and epigenetic regulation during developmental and pathological stages. In addition, we discuss possible application of these information in regeneration of bone and cartilage.

Endochondral ossification plays critical roles in skeletal development and tissue patterning. Disruption of endochondral ossification and cartilage homeostasis results in skeletal dysplasia and cartilage diseases such as osteoarthritis. Several transcription factors regulate chondrocyte differentiation and expression of chondrogenic matrices, and consequently maintains order of endochondral ossification. In this review article, we would like to introduce recent advancement in understanding of role and functional regulation of transcription factors in endochondral ossification.

Bone formation is the key for successful dental treatments including periodontal tissue regeneration osseointegration of implant placement in which new alveolar bone formation is mandatory. Parathyroid hormone (PTH) is a peptide hormone containing 84 amino acids. Accumulated results show that intermittent PTH administration increases bone mass. Accordingly, recombinant N-terminal fragment of human PTH (1-34) , Teriparatide, is used for the treatments of osteoporosis worldwide. It is, therefore, expected that PTH has the potential to be a new therapeutic intervention for oral diseases that require increased bone remodeling and new bone formation.

Bone pain is the most common complications in bone metastases, causing increased morbidity and undermining quality of life (QOL) in patients. It has been considered that algesic factors produced by tumor tissues and nerve injury are involved in pain progression. However, the molecular mechanisms of bone pain are still complex and not fully understood. Recent studies show that acidic microenvironment created in bone metastasis is relevant to pain signal through the activation of acid-sensing nociceptor in sensory neurons. These elucidations might be lead to the development of therapeutic approaches for cancer pain.

Bone is one of the most preferential metastatic target sites for cancers. However, based on the anatomical structure of the vascular system, bone is not recognized as a preferential metastatic target. Therefore, the biological crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Bone microenvironments possess unique biological features characterized by abundant growth factors and diverse cellular network including osteoblasts, osteoclasts and hematopietic cells. Cancers develop bone metastases by utilizing these unique bone environments for colonization and bone destruction. Better understandings of precise molecular mechanisms underlying cancer and bone crosstalk would contribute to the development of new therapeutic approaches for the treatment of bone metastasis at molecular levels.

Clinically, fatty marrow, accumulation of adipocytes in bone marrow, is often observed in the patients who manifest bone diseases such as osteoporosis. Since adipocytes and osteoblasts are differentiated from mesenchymal stem cells, it would be clinically and biologically important to understand regulatory mechanisms of the balance between adipogenesis and osteoblastogenesis. Recently, experimental findings indicated the involvement of adipokines including leptin and adiponectin in bone metabolisms. Thus, adipocytes appear to play a role in regulation of bone metabolisms.

Bone is a complex tissue which contains osteoclasts, osteoblasts, chondrocytes, adipocytes, hematopoietic cells and immune cells. Since osteoblasts share the same origin with adipocytes in bone marrow cavity, it is assumed that PPAR (peroxisome proliferator-activated receptor) family, which is an important nuclear receptor family for adipocyte differentiation, plays a role in the bone microenvironment. Indeed, recent evidences support the primitive roles of PPAR family in osteoblast differentiation as well as adipocyte differentiation. Furthermore, PPAR family is also implicated in the regulation of differentiation and function of osteoclasts. Here, we summarized the functional roles of PPAR family in bone remodeling and regulation of bone microenvironments. We also discuss the potential mechanisms that regulate expression and function of PPAR family during bone metabolisms.