MU MUSCLE-BO BONE CR CROSS SSTALK IN IN B BURN IN INJU JURY - - PowerPoint PPT Presentation

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

EPIDERMIS BURN INJURY

INFLAMMATION GLUCOCORTICOIDS

BONE RESORPTION MUSCLE WASTING TGFβ

SE SEVERE B BURN I INJURY I INITIATES S S SYSTEMI MIC I INFLA LAMMA MMATORY A AND A ACUTE ST STRESS RESPONSES

5d post-burn 2d control Backscatter SEM 1 2 3 1 2 3

BONE E RESORPTIO TION BEGIN INS ON DAY 1POST-BUR URN

SI SINGLE LE-DO DOSE B BISPHOSPHONATE P PREVENTS R RESORPTIVE B BONE L LOSS FO FOR UP TO 2 YEARS

100 200 300 400

RA (nmol/min/100ml leg volume) (n=10) * pamidronate control

• 150
• 50

50 150 250 350

NB (nmol/min/100ml leg volume) (n=7) (n=10) * * P = 0.024 pamidronate control (n=7)

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 IS ISOTOPE STUD UDIE IES

N B B+P N B B+P MyHC IF staining in myotubes MyHC IF staining in myotubes

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

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%

N B B + P

5 1 0 1 5 2 0

M y o tu b e s iz e u m

* *

#

N B B + P

5 1 0 1 5 2 0 2 5

M y o tu b e s iz e u m

* * * #

B B+P B+Anti-TGFβ B+P+Anti-TGFβ

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

MY MYOTUBE SI SIZE R RESC SCUE B BY A ANTI-TG TGFβ IN IN BUR URNED CONTROLS

B B + A n t i

• T

G F b B + P B + P + A n t i

• T

G F b

5 1 0 1 5 2 0 2 5

M y o tu b e s iz e u m ** ** ***

B B + A n ti-T G Fb B + P B + P + A n ti-T G Fb

0 .0 0 .5 1 .0 1 .5

p S M A D A .U . * *

EPIDERMIS BURN INJURY INFLAMMATION GLUCOCORTICOI DS BONE RESORPTION MUSCLE WASTING TGFβ EPIDERMIS BURN INJURY INFLAMMATION GLUCOCORTICOI DS BONE RESORPTION MUSCLE WASTING TGFβ PAMIDRONATE

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

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