bims-smemid 2023-09-10 papers

Joint Bone Spine. 2023 Sep 06. pii: S1297-319X(23)00113-6. [Epub ahead of print] 105634

Metabolic reprogramming of glycolysis favors cartilage progenitor cells rejuvenation: a potential therapeutic for Osteoarthritis.

Jianming Shi, Guihua Du.

Osteoarthritis (OA), the leading cause of disability in the elderly, still lacks effective treatment due to the unelucidated mechanisms of pathogenesis and progression. In cartilage, although the solo cell type of chondrocytes is resident, cartilage progenitor cells (CPCs) are identified. Chondrocytes in cartilage mainly utilize glycolysis because of the low oxygen tension. Until now, whether the metabolic pathway changes are associated with OA initiation or progression, as well as the biology of CPCs, remains fully clarified. By reviewing relevant literature from previous functional studies, we further mined recently published mouse and human chondrocytes single-cell RNA-sequencing datasets to explore gene expression profiles shift in OA initiation or during OA progression, regarding metabolism. In this review, we demonstrated that chondrocytes' metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) in OA initiation or during OA progression. Genes that related to OXPHOS, electron transport, mitochondrial translation, and mitochondrial respiratory chain complex assembly were upregulated in chondrocytes of injured cartilage or during OA progression. In addition, compared to OXPHOS, glycolysis facilitates CPC expansion and chondrogenic potential. The collated information suggests a potential therapeutic for OA through metabolic reprogramming of glycolysis to interrupt OA pathology and favor CPCs rejuvenation to restore healthy cartilage.

Keywords: Chondrocyte; Glycolysis; Osteoarthritis; Oxidative phosphorylation

DOI: https://doi.org/10.1016/j.jbspin.2023.105634

BMB Rep. 2023 Sep 08. pii: 5966. [Epub ahead of print]

Mitochondrial transplantation: an overview of a promising therapeutic approach.

Ji Soo Kim, Seonha Lee, Won-Kon Kim, Baek-Soo Han.

Mitochondrial transplantation is a promising therapeutic approach for the treatment of mitochondrial diseases caused by mutations in mitochondrial DNA, as well as several metabolic and neurological disorders. Animal studies have shown that mitochondrial transplantation can improve cellular energy metabolism, restore mitochondrial function, and prevent cell death. However, challenges need to be addressed, such as the delivery of functional mitochondria to the correct cells in the body, and the long-term stability and function of the transplanted mitochondria. Researchers are exploring new methods for mitochondrial transplantation, including the use of nanoparticles or CRISPR gene editing. Mechanisms underlying the integration and function of transplanted mitochondria are complex and not fully understood, but research has revealed some key factors that play a role. While the safety and efficacy of mitochondrial transplantation have been investigated in animal models and human trials, more research is needed to optimize delivery methods and evaluate long-term safety and efficacy. Clinical trials using mitochondrial transplantation have shown mixed results, highlighting the need for further research in this area. In conclusion, although mitochondrial transplantation holds significant potential for the treatment of various diseases, more work is needed to overcome challenges and evaluate its safety and efficacy in human trials.

Nephrol Dial Transplant. 2023 Sep 02. pii: gfad188. [Epub ahead of print]

The basics of phosphate metabolism.

Carsten A Wagner.

Phosphorus is an essential mineral that is under the form or inorganic phosphate (Pi) required for building cell membranes, DNA and RNA molecules, for energy metabolism, signal transduction or pH buffering. In bone, Pi is essential for bone stability under the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, passive absorption depends mostly on bioavailability. Renal excretion is controlling systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be also tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake, metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphatemia or hyperphosphatemia as evident from inborn or acquired diseases. This review provides an integrated overview over the biology of phosphate and Pi in the mammalian organism.

Keywords: bone; cell metabolism; endocrine regulation; intestine; kidney

DOI: https://doi.org/10.1093/ndt/gfad188