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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.

One of the major topics of ASBMR in this year was progress in research on "Bone and muscle crosstalk". It has been practically and clinically known that appropriate exercise has good effects on bones strength, however the mechanism is still elusive. In this ASBMR meeting, there were many reports that muscle-derived hormones, e.g. Irisin, β-aminoisobutyric acid(BAIBA)or Myostatin interact with skeletal cells. Especially, the report regarding Irisin was impressive. Moreover, several reports regarding new aspects of osteoblasts and bone formation were also interesting. In this report, we would like to introduce these interesting abstracts.

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.

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.

Differentiation process of osteoblasts, which play a central role in bone formation, is harmoniously controlled by several cytokines and hormones. Particularly, Bone Morphogenetic Protein (BMP) , Indian Hedgehog (Ihh) , and Wnt family proteins are important cytokines for osteoblast differentiation. Understandings of molecular mechanisms by which these cytokines stimulate osteoblast differentiation have been extensively investigated. BMP/Smad signaling, canonical Wnt pathway, non-canonical Wnt pathway and Ihh/Gli signaling play critical role in osteoblast differentiation. Furthermore, biochemical and genetic studies have demonstrated important roles of Runt related transcription factor 2 (Runx2) , Osterix, Activating transcription factor 4 (ATF4) , Msh homeobox 2 (Msx2) and Oasis for osteoblast differentiation. Thus, these milestone studies have dramatically progressed in our understanding of the cellular and molecular mechanisms of osteoblast differentiation for 20 years.

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.

Recently, large body of evidences that Wnt plays an important role in regulation of tissue patterning and skeletogenesis including membranous and enchondral ossification is accumulating. Several genetic studies also indicate that low density lipoprotein receptor related protein (LRP) 5, LRP6, beta-catenin and lymphoid enhancer-binding factor/T-cell factor (LEF/TCF) participate in osteogenic action induced by Wnt family members. In contrast, secreted Frizzled-related proteins and dickkopf (Dkk) proteins, natural Wnt inhibitory factors, inhibit Wnt-dependent osteogenesis, presumably functioning as a negative feedback loop. In addition, Wnt signaling interacts with BMP signaling, thereby modulating its osteogenic action. Thus, the network systems of Wnt signaling temporally and spatially controls osteogenic action of Wnt family members.

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.