Beta2-adrenergic agonist-induced hypertrophy of the quadriceps skeletal muscle does not modulate disease severity in the rodent meniscectomy model of osteoarthritis.
OBJECTIVE
To examine whether beta2-adrenergic agonist-induced hypertrophy of the quadriceps skeletal muscle can modulate the severity of osteoarthritis (OA) in the rodent meniscectomy (MNX) model.


METHODS
Male Lewis rats were subcutaneously administered with 1.5 mg/kg/day clenbuterol hydrochloride (n=15) or saline vehicle (n=20) for 14 days. Following pre-treatment, five animals from each group were sacrificed to assess the immediate effects of clenbuterol. The remaining animals underwent either invasive knee surgery (clenbuterol pre-treated n=10; saline pre-treated n=10) or a sham control surgical procedure (saline pre-treated n=5). During disease initiation and progression, weight bearing was assessed by hindlimb loading. Myosin heavy chain (MHC) protein isoforms were quantified by silver stained SDS PAGE. OA severity was graded by assessment of toluidine blue stained step coronal sections of the total knee joint.


RESULTS
Clenbuterol treatment resulted in an increase in total bodyweight, growth rate and in quadriceps skeletal muscle mass. Meniscal surgery resulted in the development of OA-like lesions, changes to weight bearing, and changes in MHC protein expression in the quadriceps. Clenbuterol-induced skeletal muscle hypertrophy had no effect on either weight bearing or articular pathology following MNX surgery.


CONCLUSIONS
Our data reveal that clenbuterol-induced skeletal muscle hypertrophy is unable to mimic the beneficial clinical effects of increased musculature derived through targeted strength training in humans, in a rodent model of MNX-induced OA. In addition we observed fibre-type switching to "slow twitch" in the quadriceps muscle during the induction of OA that warrants further investigation as to its relationship to joint stability.
Tonge
D P
DP
Nutritional Sciences, School of Biosciences, Sutton Bonington Campus, Sutton Bonington, University of Nottingham, LE12 5RD, UK. sbxdpt@nottingham.ac.uk
Jones
S W
SW
Parr
T
T
Bardsley
R
R
Doherty
M
M
Maciewicz
R A
RA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002976:Clenbuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000139:chemically induced*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis; D010003:Osteoarthritis / Q000188:drug therapy* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew / Q000254:growth & development; D016474:Weight-Bearing / Q000502:physiology
D000318:Adrenergic beta-Agonists; D018995:Myosin Heavy Chains; D002976:Clenbuterol