The mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that integrates inputs from nutrients and growth factors to control many fundamental cellular processes through two distinct protein complexes mTORC1 and mTORC2. Recent mouse genetic studies have established that mTOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. In addition, mTORC1 has emerged as a common effector mediating the bone anabolic effect of Igf1, Wnt and Bmp. Dysregulation of mTORC1 could contribute to various skeletal diseases including osteoarthritis and osteoporosis. Here we review the current understanding of mTOR signaling in skeletal development and bone homeostasis, as well as in the maintenance of articular cartilage. We speculate that targeting mTOR signaling may be a valuable approach for treating skeletal diseases.

Skeletal stem/progenitor cells (SSPCs) can differentiate into osteogenic or adipogenic lineage. The mechanism governing lineage allocation of SSPCs is still not completely understood. Hedgehog (Hh) signaling plays an essential role in specifying osteogenic fate of mesenchymal progenitors during embryogenesis. However, it is still unclear whether Hh signaling is required for lineage allocation of SSPCs in postnatal skeleton, and whether its dysregulation is related to age-related osteoporosis. Here, we demonstrated that Hh signaling was activated in metaphyseal SSPCs during osteogenic differentiation in the adult skeleton, and its activity decreased with aging. Inactivation of Hh signaling by genetic ablation of Smo, a key molecule in Hh signaling, in Osx-Cre-targeted SSPCs and hypertrophic chondrocytes led to decreased bone formation and increased bone marrow adiposity, two key pathological features of age-related osteoporosis. Moreover, we found that the bone-fat imbalance phenotype caused by Smo deletion mainly resulted from aberrant allocation of SSPCs toward adipogenic lineage at the expense of osteogenic differentiation, but not due to accelerated transdifferentiation of chondrocytes into adipocytes. Mechanistically, we found that Hh signaling regulated osteoblast versus adipocyte fate of SSPCs partly through upregulating Wnt signaling. Thus, our results indicate that Hh signaling regulates bone homeostasis and age-related osteoporosis by acting as a critical switch of cell fate decisions of Osx-Cre-targeted SSPCs in mice and suggest that Hh signaling may serve as a potential therapeutic target for the treatment of osteoporosis and other metabolic bone diseases.

Chickpea protein isolate (CPI) is a promising dietary protein with the advantages of low allergenicity, easy digestion and balanced composition of essential amino acids. However, due to the thick skin of chickpeas, the extraction of CPI is challenging, resulting in lower efficiency of the alkaline extraction-isoelectric precipitation (AE-IEP) method. Therefore, the present study investigated the effect of pulsed electric field combined with ultrasound (PEF-US) treatment on the extraction efficiency of CPI and the functional properties was characterized. Parameter optimization was carried out using response surface methodology (RSM), with the following optimized conditions: pulse duration of 87 s, electric field intensity of 0.9 kV/cm, ultrasonic time of 15 min, and ultrasonic power of 325 W. Under the optimized conditions, the yield of CPI after combined (PEF-US) treatment was 13.52 ± 0.13 %, which was a 47.28 % improvement over the AE-IEP method. This yield was better than that obtained with either individual PEF or US treatment. Additionally, the functional properties (solubility, emulsification, and foaming) of CPI were significantly enhanced compared to AE-IEP. However, the stability of emulsification and foaming did not show significant differences among the four methods. The PEF-US method efficiently extracts CPI with excellent functional properties, enabling the production of proteins as desired functional additives in the food industry.