Characterization of dynamic changes in Matrix Gla Protein (MGP) gene expression as function of genetic risk alleles, osteoarthritis relevant stimuli, and the vitamin K inhibitor warfarin.

OBJECTIVE: We here aimed to characterize changes of Matrix Gla Protein (MGP) expression in relation to its recently identified OA risk allele rs1800801-T in OA cartilage, subchondral bone and human ex vivo osteochondral explants subjected to OA related stimuli. Given that MGP function depends on vitamin K bioavailability, we studied the effect of frequently prescribed vitamin K antagonist warfarin. METHODS: Differential (allelic) mRNA expression of MGP was analyzed using RNA-sequencing data of human OA cartilage and subchondral bone. Human osteochondral explants were used to study exposures to interleukin one beta (IL-1ß; inflammation), triiodothyronine (T3; Hypertrophy), warfarin, or 65% mechanical stress (65%MS) as function of rs1800801 genotypes. RESULTS: We confirmed that the MGP risk allele rs1800801-T was associated with lower expression and that MGP was significantly upregulated in lesioned as compared to preserved OA tissues, mainly in risk allele carriers, in both cartilage and subchondral bone. Moreover, MGP expression was downregulated in response to OA like triggers in cartilage and subchondral bone and this effect might be reduced in carriers of the rs1800801-T risk allele. Finally, warfarin treatment in cartilage increased COL10A1 and reduced SOX9 and MMP3 expression and in subchondral bone reduced COL1A1 and POSTN expression. DISCUSSION & CONCLUSIONS: Our data highlights that the genetic risk allele lowers MGP expression and upon OA relevant triggers may hamper adequate dynamic changes in MGP expression, mainly in cartilage. The determined direct negative effect of warfarin on human explant cultures functionally underscores the previously found association between vitamin K deficiency and OA.

Avulsion fracture of the supinator crest as an indication for a sustained posterolateral (sub)luxation of the elbow. A case report, anatomical evaluation and review of the literature.

The treatment of elbow injuries can be challenging because of the complexity of both anatomy and pathology. We present a rare traumatic avulsion fracture of the supinator crest of the ulna in a 37-year-old patient. Conservative treatment in a long arm cast for four weeks led to satisfactory results. Reproduction of the fracture on a cadaveric elbow clarified that the avulsed fragment holds the insertion of the lateral ulnar collateral ligament (LUCL). The mechanism of trauma that causes this fracture is a posterolateral (sub) luxation of the elbow, which usually causes the LUCL to rupture, but in rare cases the insertion of this ligament can be avulsed. A posterolateral (sub) luxation of the elbow can lead to chronic posterolateral rotational instability and therefore the stability of the elbow should be taken into account in the treatment of patients with such a fracture. A review of the literature concluded that this fracture often is associated with other injuries to the elbow and that it is easily missed on conventional AP and lateral radiographs. CT or MRI imaging and a radial head-capitellum view radiograph can be beneficial. Both conservative and operative treatments have been described with good clinical results.