MU MUSCLE-BO BONE CR CROSS SSTALK IN IN B BURN IN INJU JURY Gordon L. Klein MD MPH Department of Orthopaedic Surgery and Rehabilitation University of Texas Medical Branch Galveston, Texas USA
SEVERE B SE BURN I INJURY I INITIATES S S SYSTEMI MIC I INFLA LAMMA MMATORY A AND A ACUTE ST STRESS RESPONSES BURN INJURY EPIDERMIS INFLAMMATION GLUCOCORTICOIDS BONE RESORPTION MUSCLE WASTING TGFβ
BONE E RESORPTIO TION BEGIN INS ON DAY 1POST-BUR URN 5d post-burn 1 2 3 Backscatter SEM 2d control 1 2 3
SI SINGLE LE-DO DOSE B BISPHOSPHONATE P PREVENTS R RESORPTIVE B BONE L LOSS FO FOR UP TO 2 YEARS
BIS ISPHO HOSPHO HONATE TE TR TREATED TED BUR URN PATIEN TIENTS HA HAVE E LOWER WER MUS USCLE E PR PROTEIN BREAKDOWN AND PO POSITIVE NET BALANCE ON STABLE ISOTOPE STUD IS UDIE IES 350 NB (nmol/min/100ml leg volume) RA (nmol/min/100ml leg volume) 400 (n=10) * 250 300 * P = 0.024 150 200 (n=10) * 50 (n=7) 0 100 (n=7) -50 0 -150 control pamidronate control pamidronate
MU MURINE C C2C12 MY MYOBLA LASTS C S CULTURED I IN SE SERUM F M FROM B M BURN P PATIENTS + S +/- BIS ISPHO HOSPHO HONATE TES SHO HOW W PARTIA TIAL MYOTUB TUBE E DIA IAMETER ETER RESCUE UE WITH WITH BP MyHC IF staining in myotubes N B+P B MyHC IF staining in myotubes N B B+P
MY MYOTUBE SI SIZE A AFTER C CULTURE W WITH SE SERUM F M FROM N M NORMA MAL, B BURNED CO CONTROLS AND BURNED + BISPHOSPHONATE TREATMENT AT 1% AND 5% M y o tu b e s iz e M y o tu b e s iz e 2 5 2 0 2 0 # 1 5 * # * * 1 5 * * u m u m 1 0 1 0 5 5 0 0 P N B B + P N B + B
MY MYOTUBES AFTER CULTURE IN SERUM M FROM M BURNED CONTROLS WITH ADDED ANTI- TG TGFβ RE RESCUED ED SIZE E TO BE E COMPARAB ARABLE E TO BISPHOSPHONATE TE TRE TREATM TMEN ENT T B+Anti-TGFβ B B+P B+P+Anti-TGFβ
MY MYOTUBE SI SIZE R RESC SCUE B BY A ANTI-TG TGFβ IN IN BUR URNED CONTROLS p S M A D M y o tu b e s iz e 1 .5 2 5 ** *** ** 2 0 1 .0 A .U . 1 5 * u m * 1 0 0 .5 5 0 .0 0 B + A n ti-T G F b B + P + A n ti-T G F b B B + P b b P B F F + G G B T T - - i i t t n n A A + + P B + B
BONE E RESORPTIO TION LIB IBER ERATE TES TGFβ THA THAT T STI TIMUL ULATE TES UB UBIQUI UITI TIN=MED EDIATED TED CATABOLIS ISM AND SUP UPPRESSES PHO HOSPHO HORYLATIO TION OF F AKT/m TOR ANABOLIC IC PA PATHWAY, BLOCKED BY BISPHOSPHONATE BURN INJURY BURN INJURY EPIDERMIS EPIDERMIS INFLAMMATION INFLAMMATION GLUCOCORTICOI GLUCOCORTICOI DS DS BONE BONE MUSCLE WASTING MUSCLE WASTING RESORPTION RESORPTION TGFβ TGFβ PAMIDRONATE
ACKNOW OWLEGEMENTS • This work was funded in part by NIH P50-GM60338 protocol 4 (GLK) • Collaborating investigators included: Lynda Bonewald, PhD, Fabrizio Pin PhD, and Andrea Bonetto MD PhD, Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis IN USA RE REFERE RENCES Pin F et al Front Endocrinol 2019;10:543 published 2019 Aug 7, doi: 10.3389/fendo.2019.00543 Borsheim E et al J Bone Miner Res 2014; 29: 1369-72 Klein GL et al Bone 1995; 17: 455-60
Recommend
More recommend
