Magnetic Resonance Imaging and Spectroscopy Section, National Institute on Aging, National Institutes of Health, Intramural Research Program, Baltimore, MD 21224, USA.
Osteoarthritis Cartilage. 2010 May;18(5):724-33. doi: 10.1016/j.joca.2010.01.006. Epub 2010 Feb 6.
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.
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.
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.
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.
哈特利豚鼠的关节软骨退变与特发性人类骨关节炎（OA）相似。我们研究了脉冲低强度超声（PLIUS）在哈特利豚鼠关节上的应用是否能预防或减缓这种退行性过程的进展。
在退变开始时（8 周龄）对雄性哈特利豚鼠进行治疗，以评估 PLIUS 预防 OA 的能力，或在较晚年龄（12 个月）评估 PLIUS 减缓已建立疾病进展的程度。PLIUS（30 mW/cm(2)）应用于膝关节 20 分钟/天，持续 3 至 10 个月，对侧肢体作为对照。根据改良的 Mankin 评分对关节软骨进行组织学分级，以评估治疗效果。对软骨进行白细胞介素-1 受体拮抗剂（IL-1ra）、基质金属蛋白酶（MMP）-3、MMP-13 和转化生长因子（TGF）-β1 的免疫组织化学染色，以评估这些蛋白表达的模式。
PLIUS 未能完全预防预防组的软骨退变，但减轻了疾病的严重程度，与对照组相比，治疗关节的表面不规则度明显降低，基质染色丢失程度也明显降低。PLIUS 还减缓了已建立疾病组的疾病进展，但与预防组相比，其减轻程度略小。免疫组织化学染色显示，PLIUS 治疗关节 TGF-β1 的产生明显减少。这表明内源性修复活性降低，与软骨降解程度明显降低一致。
PLIUS 具有减轻特发性人类 OA 动物模型中软骨退变进展的能力。在治疗早期而不是已建立的退变时，效果更为明显。
