Modification of osteoarthritis in the guinea pig with pulsed low-intensity ultrasound treatment.
OBJECTIVE
The Hartley guinea pig develops articular cartilage degeneration similar to that seen in idiopathic human osteoarthritis (OA). We investigated whether the application of pulsed low-intensity ultrasound (PLIUS) to the Hartley guinea pig joint would prevent or attenuate the progression of this degenerative process.


METHODS
Treatment of male Hartley guinea pigs was initiated at the onset of degeneration (8 weeks of age) to assess the ability of PLIUS to prevent OA, or at a later age (12 months) to assess the degree to which PLIUS acted to attenuate the progression of established disease. PLIUS (30 mW/cm(2)) was applied to stifle joints for 20 min/day over periods ranging from 3 to 10 months, with contralateral limbs serving as controls. Joint cartilage histology was graded according to a modified Mankin scale to evaluate treatment effect. Immunohistochemical staining for interleukin-1 receptor antagonist (IL-1ra), matrix metalloproteinase (MMP)-3, MMP-13, and transforming growth factor (TGF)-beta1 was performed on the cartilage to evaluate patterns of expression of these proteins.


RESULTS
PLIUS did not fully prevent cartilage degeneration in the prevention groups, but diminished the severity of the disease, with the treated joints showing markedly decreased surface irregularities and a much smaller degree of loss of matrix staining as compared to controls. PLIUS also attenuated disease progression in the groups with established disease, although to a somewhat lesser extent as compared to the prevention groups. Immunohistochemical staining demonstrated a markedly decreased degree of TGF-beta1 production in the PLIUS-treated joints. This indicates less active endogenous repair, consistent with the marked reduction in cartilage degradation.


CONCLUSIONS
PLIUS exhibits the ability to attenuate the progression of cartilage degeneration in an animal model of idiopathic human OA. The effect was greater in the treatment of early, rather than established, degeneration.
Gurkan
I
I
Magnetic Resonance Imaging and Spectroscopy Section, National Institute on Aging, National Institutes of Health, Intramural Research Program, Baltimore, MD 21224, USA.
Ranganathan
A
A
Yang
X
X
Horton
W E
WE
Todman
M
M
Huckle
J
J
Pleshko
N
N
Spencer
R G
RG
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014464:Ultrasonic Therapy / Q000379:methods*
D053590:Interleukin 1 Receptor Antagonist Protein; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases