ENPP1 downregulation and FGF23 upregulation in growth-related calcification of the tibial tuberosity in rats.

During tibial tuberosity growth, superficial and deep portions can be observed; however, the deep portion is not observed after the growth period, as it develops into bone tissues. Calcification in vivo is known to be constitutively suppressed by ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) but promoted by tissue-nonspecific alkaline phosphatase (TNAP). FGF23 promotes calcification of enthesis. Gene expression of FGF23 increased rapidly at 13W in this study. Therefore, the tibial tuberosity is speculated to develop via Enpp1 downregulation and Tnap upregulation; however, the understanding of these processes remains unclear. Hence, in the present study, we aimed to explore the age-related structural changes and underlying gene expression changes in the tibial tuberosity of rats. Male Wistar rats were divided into three groups (3-, 7-, and 13-week-old; eight each). The tibial tuberosity superficial and deep portions were clearly observed in 3- and 7-week-old rats, but the presence of the deep portion was not confirmed in 13-week-old rats. The extracellular matrix of hypertrophic chondrocytes was calcified. Furthermore, the Enpp1 expression was the highest in 3-week-old rats and decreased with growth. The TNAP expression did not differ significantly among the groups. The deep portion area was significantly lower in 3-week-old rats than in 7-week-old rats. Generally, the extracellular matrix of the immature chondrocytes is not calcified. Therefore, we speculated that the cartilaginous tibial tuberosity calcifies and ossifies with growth. The Enpp1 expression decreased with growth, whereas the Tnap expression remained unchanged. Thus, we surmise that the tibial tuberosity calcifies with growth and that this process involves Enpp1 downregulation and FGF23 upregulation. As Osgood-Schlatter disease is closely related to the calcification of the tibial tuberosity, these findings may help clarify the pathogenesis of this disease.

Eccentric contractions during downhill running induce Osgood‒Schlatter disease in the tibial tuberosity in rats: a focus on histological structures.

Osgood-Schlatter disease (OSD), a condition that affects adolescents, causes inflammation, pain, and prominence at the tibial tuberosity. The causes of OSD are not well understood, but eccentric contractions in the quadriceps have been suggested as a possible factor. To investigate this, a study was conducted in which 24 rats were divided into two groups: the downhill treadmill running (DR) group and the control (CO) group. The DR group underwent a preliminary running program for 1 week, followed by a main running program for 3 weeks. The results showed that the deep region of the tibial tuberosity in the DR group was larger than that in the CO group, and inflammatory cytokines involved in gene expression were upregulated in the DR group. The anterior articular cartilage and deep region in the DR group were also immunoreactive to substance P. Additionally, high-activity chondrocytes of small size were observed in the non-calcified matrix. Thus, the DR group exhibited symptoms similar to OSD, including inflammation, pain, and prominence. These findings suggest that eccentric contractions in the quadriceps may play a role in the development of OSD. Further research is needed to better understand the pathophysiology of this condition and develop effective treatment options.

Vector potential dual effect of promoting the proliferation of chondrocytes and inhibiting the calcification process in the articular cartilage.

OA commonly affects the articular cartilage of the tibia, and its calcification worsens its advancement and its prevalence has recently increased. Vector potential (VP) represents a novel physical therapy for treating OA. Since the impact of VP on articular cartilage remains unknown, we aimed to assess its effects on articular cartilage and its potential as a new treatment for OA. Here, we divided 24 male Wistar rats, 6-week-old, into control (CO, n = 12) and VP stimulus (n = 12) groups (VP conditions: volt, 67 mV; frequency, 20 kHz; current, 0.12 mA; experimental frequency, 30 min/days, 5 days/week, and 3 weeks). Articular cartilage can be classified into four layers: superficial, medial, deep, and calcified. Moreover, the number of chondrocytes in the articular cartilage was higher in the CO group compared to the VP group, although the calcified layer was thinner in the VP group. Furthermore, MKi67 exhibited higher expression in the VP group than in the CO group, while ectonucleotide pyrophosphatase/phosphodiesterase 1 was downregulated in the VP group. Our findings indicate that VP positively influenced chondrocyte proliferation and inhibited calcification in articular cartilage. Thus, VP stimulation may assist in the development of novel strategies for preventing OA.