Transection of the canine anterior cruciate ligament (ACLT) is a well- established means of inducing osteoarthritis (OA), which develops slowly and is mild for the first 2-3 years after surgery. However, the progression of OA can be greatly accelerated if hind limb deafferentation, accomplished by ipsilateral dorsal root ganglionectomy (DRG), precedes ACLT. Since dogs with stable joints do not develop joint pathology after DRG, it seems likely that the nervous system uses 2 separate mechanisms to protect joints: 1) stable joints are protected by centrally programmed mechanisms that do not depend upon proprioceptive or nociceptor information from ipsilateral sensory nerves; and 2) unstable and/or injured joints are protected from rapid breakdown by sensory information carried by ipsilateral nerves. In both cases, it is likely that co-ordinated muscular activity (protective muscular reflexes, or PMRs) is responsible for maintaining the range of excursion within the safest possible limits, thereby protecting the joint. The purpose of this study is to determine if alterations in kinematics and electromyography (EMG) can be used to investigate the mechanisms by which sensory nerves control neuromuscular reflexes that protect joints. Four groups of 7 dogs will be used: Group A will undergo unilateral ACLT to destabilize the knee joint; Group B will undergo sham ACLT; Group C will undergo unilateral DRG to deafferent the hind limb; Group D will undergo sham DRG. All animals will be trained to locomote on a motor-driven treadmill. Kinematic and EMG evaluations will be performed preoperatively, and at 4, 8, 12, and 24 weeks postoperatively. The kinematic evaluation will use high-speed films to examine changes in joint angular excursion and velocity patterns as well as stance/swing relationships, whereas the EMG analysis will examine changes in muscle amplitude and on-off patterns. These changes will be regarded as the """"""""normal"""""""" response of the neuromuscular system to ACLT and DRG, and will provide baseline information critical for future experiments designed to determine how the nervous system organizes PMRs and protects joints.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Mazzuca, Steven A; Brandt, Kenneth D; Katz, Barry P et al. (2007) Risk factors for early radiographic changes of tibiofemoral osteoarthritis. Ann Rheum Dis 66:394-9
Merle-Vincent, F; Vignon, E; Brandt, K et al. (2007) Superiority of the Lyon schuss view over the standing anteroposterior view for detecting joint space narrowing, especially in the lateral tibiofemoral compartment, in early knee osteoarthritis. Ann Rheum Dis 66:747-53
Otterness, Ivan G; Brandt, Kenneth D; Le Graverand, Marie-Pierre Hellio et al. (2007) Urinary TIINE concentrations in a randomized controlled trial of doxycycline in knee osteoarthritis: implications of the lack of association between TIINE levels and joint space narrowing. Arthritis Rheum 56:3644-9
Mazzuca, S A; Brandt, K D; Eyre, D R et al. (2006) Urinary levels of type II collagen C-telopeptide crosslink are unrelated to joint space narrowing in patients with knee osteoarthritis. Ann Rheum Dis 65:1055-9
Brandt, Kenneth D; Mazzuca, Steven A (2006) Experience with a placebo-controlled randomized clinical trial of a disease-modifying drug for osteoarthritis: the doxycycline trial. Rheum Dis Clin North Am 32:217-34, xi-xii
Mazzuca, S A; Brandt, K D; Katz, B P et al. (2006) Comparison of quantitative and semiquantitative indicators of joint space narrowing in subjects with knee osteoarthritis. Ann Rheum Dis 65:64-8
Mazzuca, Steven A; Poole, A Robin; Brandt, Kenneth D et al. (2006) Associations between joint space narrowing and molecular markers of collagen and proteoglycan turnover in patients with knee osteoarthritis. J Rheumatol 33:1147-51
Mikesky, Alan E; Mazzuca, Steven A; Brandt, Kenneth D et al. (2006) Effects of strength training on the incidence and progression of knee osteoarthritis. Arthritis Rheum 55:690-9
Hellio Le Graverand, M-P; Brandt, K D; Mazzuca, S A et al. (2006) Association between concentrations of urinary type II collagen neoepitope (uTIINE) and joint space narrowing in patients with knee osteoarthritis. Osteoarthritis Cartilage 14:1189-95
Brandt, Kenneth D; Mazzuca, Steven A (2005) Lessons learned from nine clinical trials of disease-modifying osteoarthritis drugs. Arthritis Rheum 52:3349-59

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