The Therapeutic Effect of rhMK on Osteoarthritis in Mice, Induced by Destabilization of the Medial Meniscus

Abstract

Osteoarthritis (OA) is a worldwide disease in aged people, causing not only physical suffering to the patients themselves, but also a great burden on their families and on society. Here we used a mouse OA model induced by destabilization of the medial meniscus (DMM), and studied the therapeutic effect of recombinant human midkine (rhMK) on this OA model. Our results indicated that the DMM surgery induced mechanical allodynia and locomotor activity obstacles, together with cartilage injury in the C57BL/6 mice. The rhMK treatment mitigated the OA related mechanical allodynia, improved locomotor activity capacity, and prevented degradation of the cartilage. Considering the safety issue of rhMK used as a biologic, we also inspected the main organs in the rhMK treated mice throughout the process and found no pathological change. These results suggest that rhMK could be used as a biologic to treat OA or OA related pain.

Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model

“…Destabilization of the medial meniscus (DMM) surgery was performed as previously described 33 – 35 using 10-week-old male WT and Hyal2 −/− mice. Briefly, mice were anesthetized with a 0.1 ml intraperitoneal injection of pentobarbital sodium (10 mg/ml).…”

Midkine is overexpressed in acute pancreatitis and promotes the pancreatic recovery in L‐arginine‐induced acute pancreatitis in mice

“…Recombinant human MK was expressed and purified as previously reported and has been used to investigate its effect on osteoarthritis in mice and rats. The results of these studies show that rhMK stimulates proliferation of primary articular chondrocytes in vitro and in vivo , which could be a proof that rhMK has cross‐reaction with the same mice . Thus, rhMK was applied to detect the effect of MK on the recovery of pancreatic lesion in mice in the present study.…”

“…The results of these studies show that rhMK stimulates proliferation of primary articular chondrocytes in vitro and in vivo, which could be a proof that rhMK has crossreaction with the same mice. 26,27 Thus, rhMK was applied to detect the effect of MK on the recovery of pancreatic lesion in mice in the present study. The pancreatic recovery could be promoted in L-arginine-induced pancreatitis by rhMK treatment.…”

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis

“…3a,b ), we focused on HSP70 (encoded by HSPA1A and HSPA1B ) and midkine (encoded by MDK ) because these two proteins were previously reported to be implicated in chondrocyte biology, and over-expression of HSP70 (ref. 35 ) and treatment with recombinant midkine 36 have been reported to protect against OA. After treatment with selective Na v 1.7 blockers and the pan-Na v blocker CBZ, which is known to act on Na v 1.7 (ref.…”