CK2.1, a novel peptide, induces articular cartilage formation in vivo.
Bone morphogenetic protein 2 regulates chondrogenesis and cartilage formation. However, it also induces chondrocyte hypertrophy and cartilage matrix degradation. We recently designed three peptides CK2.1, CK2.2, and CK2.3 that activate the BMP signaling pathways by releasing casein kinase II (CK2) from distinct sites at the bone morphogenetic protein receptor type Ia (BMPRIa). Since BMP2 is a major regulator of chondrogenesis and the peptides activated BMP signaling in a similar way, we evaluated the effect of these peptides on chondrogenesis and cartilage formation. C3H10T1/2 cells were stimulated with CK2.1, CK2.2, and CK2.3 and evaluated for the chondrogenic and osteogenic potential. For chondrogenesis, Alcian blue staining was performed. Additionally, collagen types II and X expression was measured. For osteogenesis, osteocalcin and von Kossa staining were performed. From the three peptides, CK2.1 was the most promising peptide to induce chondrogenesis but not osteogenesis. To investigate the effect of CK2.1 on articular cartilage formation in vivo, we injected CK2.1 into the tail vein of mice. Injection of CK2.1 into the tail vein of mice led to increased articular cartilage formation but not BMD. In sharp contrast, injection of BMP2 led to increased BMD and expression of collagen type X, a marker of chondrocyte hypertrophy. MMP13 expression was unchanged. Our study demonstrates that CK2.1 drives chondrogenesis and cartilage formation without induction of chondrocyte hypertrophy. Peptide CK2.1 may, therefore, be a valuable therapeutic for cartilage degenerative diseases. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:876-885, 2017.
Department of Biological Sciences, University of Delaware, Newark, Delaware, 19716.
Hemanth
H
Akkiraju
Department of Biological Sciences, University of Delaware, Newark, Delaware, 19716.
Jeremy
J
Bonor
Department of Biological Sciences, University of Delaware, Newark, Delaware, 19716.
Anja
A
Nohe
D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D020219:Chondrogenesis / Q000502:physiology; D005260:Female; D006984:Hypertrophy / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010012:Osteogenesis / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D051785:Smad Proteins / Q000378:metabolism
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D010455:Peptides; D051785:Smad Proteins; D047390:Casein Kinase II; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
bone morphogenetic protein 2; cartilage; casein kinase 2; hypertrophy; peptide