Recombinant human midkine stimulates proliferation of articular chondrocytes

Abstract

Our results demonstrate that rhMK stimulates proliferation of primary articular chondrocytes in vitro and in vivo. The results of this study warrant further examination of rhMK for treatment of animal models of articular cartilage defects.

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

“…4a). One explanation for this might be that rhMK promotes the regeneration of the cartilage, 24,25) while the etiology, destabilized medial meniscus always exist during the process and make the neonatal chondrocytes and cartilage matrix disorganized.…”

“…24) In the DMM OA model, rhMK treatment also benefited the repair of the cartilage injury especially for the cellularity and cartilage staining but not for the structure and tidemark integrity, which might be because the etiology, DMM always exist in this DMM OA model, making the neonatal cartilage continuously in a turn-over state without ordered organization. What is exiting to us is that rhMK treatment attenuated the allodynia and therefore increased the physical activity behavior of the OA mice.…”

“…reported not only stimulating the proliferation and attenuating the differentiation of monolayer cultured chondrocyte in vitro, 24,25) but also increasing the thickness of the hyaline cartilage in vivo. 24) In the DMM OA model, rhMK treatment also benefited the repair of the cartilage injury especially for the cellularity and cartilage staining but not for the structure and tidemark integrity, which might be because the etiology, DMM always exist in this DMM OA model, making the neonatal cartilage continuously in a turn-over state without ordered organization.…”

“…[20][21][22] MK and PTN not only play an important role in nervous system formation at the embryo stage 6) but also maintain its functions at the adult stage by protecting the injured neuron from apoptosis, preventing degradation of the peripheral and central nerves and promoting the regeneration and new synapses formation of the neuron. 23) MK also have the potency for cartilage regeneration: in vitro promoting the chondrocyte proliferation and cartilage related extracellular matrix expression 24,25) and in vivo increasing the thickness of joint cartilage.…”

Functional Receptors and Intracellular Signal Pathways of Midkine (MK) and Pleiotrophin (PTN)

“…13) In addition to receptor ALK, MK and PTN also activate extracellular signal-regulated kinase (ERK1/2) and PI3K/AKT pathways through receptor RPTPζ on osteoblast-like cells 88) and through both ανβ3 and RPTPζ on HUVEC. 54) In the presence of MK, the MAPK and PI3K/AKT pathways participate in injured tissues recovery process, like the recovery of ischemic myocardial injury, [23][24][25][26][27] cartilage trauma [89][90][91] and amphetamine-induced neurotoxicity. 92) MAPK and PI3K/AKT pathways also take part in the proliferation and self-renewal of stem cells, like embryonic stem cells (ES) 20) and hematopoietic stem cell (HSC) after stimulation by PTN.…”