Calcific Tendonitis : A Model

Abstract

Calcific tendonitis is a common clinical condition associated with high rates of tendon rupture, prolonged symptoms, and poor response to therapy. Little is known about the pathogenesis of calcifications in tendons and consequently few effective therapies are available. We hypothesized that tendon calcification, like pathologic calcification in other sites, was generated by extracellular organelles known as matrix vesicles and that isolated matrix vesicles would constitute the basis for a useful model of this process. Tendon matrix vesicles were isolated from adult porcine patellar tendons using enzymatic digestion and differential centrifugation. Vesicle morphology was examined with electron microscopy. Levels of calcium, phosphate, pyrophosphate, ATP, and mineralization-associated enzymes were measured and compared with articular cartilage vesicles from porcine articular cartilage. Vesicles were embedded in agarose gels with or without type I collagen or dermatan sulfate and incubated in calcifying salt solution trace labeled with (45)calcium. (45)Calcium in the vesicle fraction was measured after 5-7 days. The type of mineral formed was determined by micro-x-ray diffraction. Matrix vesicles isolated from adult porcine tendon were similar morphologically to those obtained from articular cartilage. They contained mineralization-related enzymes and formed hydroxyapatite mineral in vitro. Mineralization was suppressed by levamisole and modulated by extracellular matrix components. Matrix vesicles isolated from tendons mineralize in vitro. This model may aid in the study of the pathogenesis of calcific tendonitis as well as serve as a means to identify effective therapies for this common disorder.

Physiopathology of intratendinous calcific deposition

“…In RCTs, degenerative changes in the extracellular matrix seem to play an important role for the formation of calcific deposits. The pathogenesis of CT involves matrix vesicles, macrophages and multinucleated giant cells with a typical osteoclast phenotype, producing a toothpaste-like material [25,29]. No vascular invasion has been documented.…”

“…This process has not been observed in other tendons. Recently, Gohr et al elucidated the role of matrix vesicles also in the patellar tendon [25], but, as the enthesis was removed, this model is more similar to a CT of the main body of the tendon than to an insertional CT. We also think that degenerative changes cannot be solely responsible, because we are not able to explain the deposition of calcium salt in twin brothers and children only with a reactive degenerative theory [65,66,71]. …”

“…Recently, matrix vesicles have been isolated in mature porcine patellar tendons [25]. Matrix vesicles are small extracellular organelles which are involved in mineralization of the extracellular matrix in many tissues, including bone and cartilage [26].…”

“…Matrix vesicles are small extracellular organelles which are involved in mineralization of the extracellular matrix in many tissues, including bone and cartilage [26]. Previous studies demonstrate the presence of matrix vesicles near calcific deposition of the RCTs [16,27], and recently they have been isolated also in the extracellular matrix of normal patellar tendons [25]. The authors pointed out the importance of extracellular matrix vesicles in pathogenetic mechanism of CT.…”

Differences between the Cell Populations from the Peritenon and the Tendon Core with Regard to Their Potential Implication in Tendon Repair

“…However, the multi-lineage differentiation potential of cells can also underlie pathological processes when differentiation is not in accordance with tissue function (ectopic differentiation) [15]. Fat deposition as well as calcification has been observed in clinical cases of tendinopathy [16], [17]. Furthermore, during extensive tissue remodeling, fibroblasts may acquire the phenotype of myofibroblasts.…”