Andersen, P. H. | bioRxiv Science

bioRxiv2024

Restoring oxidative phosphorylation enhances osteogenesis in mitochondrial DNA translation defective human bone marrow stromal cells

Bone formation is critical to maintain bone integrity. Here, we studied the importance of intact energy metabolism for bone formation in humans. The skeletal impact of impaired oxidative phosphorylation (OXPHOS) was investigated in adult individuals with genetically defective mitochondrial DNA translation (m.3243A>G). Although impaired mitochondrial ATP production in m.3243A>G human bone marrow stromal cells (hBMSC) was compensated by increased glycolytic ATP production (unchanged net ATP production), both in vitro osteoblast differentiation and in vivo ectopic bone formation were decreased. The impaired OXPHOS was associated with mitochondrial stress and disruption of the pro-osteogenic transcriptional program characteristic of hBMSC. Supporting OXPHOS pharmacologically in hBMSC restored mitochondrial ATP production, their transcriptional program and metabolism, leading to upregulation of osteogenic genes and restoration of bone formation capacity. These findings demonstrate a mitochondrial regulation mechanism of the osteogenic capacity of hBMSCs and identify OXPHOS as a potential target for increasing bone formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/629993v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@fca817org.highwire.dtl.DTLVardef@17fb2d3org.highwire.dtl.DTLVardef@b5667forg.highwire.dtl.DTLVardef@15c35db_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Equine Facial Action Coding System for determination of pain-related facial responses in videos of horses

1During the last decade, pain scales including facial expressions as indicators of pain have been developed for horses, mostly relying on direct observations or inspection of images. Despite differences in the research conditions and methodology the different scales focus on the same regions of the face, corresponding to moveable facial muscles related to the ears, eyes, nostrils, lips and chin. However, a detailed comparison of the facial activities occurring during pain is not possible. We used a Facial Action Coding System modified for horses to code and analyse video recordings from an earlier study of acute short-term experimental pain and from clinical cases with and without pain. We demonstrated for the first time EquiFACS based changes to pain in video of horses, using traditional statistical methods based on frequency, and novel analyses based on sliding observation windows and co-occurrence of facial actions. The most prominent differences of the experimental horses were related to the lower face actions chin raiser and nostril dilator, while less prominent, but significantly more frequent actions were related to the eye region, inner brow raiser (AU101), increased eye white (AD1), half blink (AU47), and ear rotator (EAD104). Ears forward (EAD101) and eye blink (AU145) were not associated to pain. Based on this we selected the two lower face actions for analysis of the clinical videos, and found that their co-occurrence within a window of 10 to 15 second gave 100% positive predictive values, as compared to the rating from three expert pain raters. Using our developed co-occurrence analyses we were surprised to detect that the chance of identifying three or more of the facial actions related to pain in 0.04 second sequence, corresponding to one frame, was below 3%, indicating that use of randomly selected images for pain scoring may be a very insensitive method.

animal behavior and cognition↗