Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy

被引:27
作者
Ruscitto, Angela [1 ]
Morel, Mallory M. [1 ]
Shawber, Carrie J. [2 ]
Reeve, Gwendolyn [3 ]
Lecholop, Michael K. [4 ]
Bonthius, Daniel [5 ]
Yao, Hai [5 ,6 ]
Embree, Mildred C. [1 ]
机构
[1] Columbia Univ, Coll Dent Med, Cartilage Biol & Regenerat Med Lab, Irving Med Ctr, New York, NY 10027 USA
[2] Columbia Univ, Coll Phys & Surg, Dept OB GYN, Div Reprod Sci,Irving Med Ctr, New York, NY USA
[3] New York Presbyterian Weill Cornell Med Ctr, Div Oral & Maxillofacial Surg, New York, NY USA
[4] Med Univ South Carolina, Dept Oral & Maxillofacial Surg, Coll Dent Med, Charleston, SC 29425 USA
[5] Clemson Univ, Clemson MUSC Bioengn Program, Dept Bioengn, Greenville, SC USA
[6] Med Univ South Carolina, Dept Oral Hlth Sci, Charleston, SC 29425 USA
关键词
angiogenesis; cartilage; chondrogenesis; miniature pigs; osteoarthritis; osteogenesis; temporomandibular joint; transdifferentiation; TEMPOROMANDIBULAR-JOINT; CONDYLAR CARTILAGE; ENDOTHELIAL-CELL; ARTICULAR-CARTILAGE; GROWTH-FACTOR; MIDDLE-EAR; PATHOGENESIS; EXPRESSION; MOUSE; DIFFERENTIATION;
D O I
10.1096/fj.201902287R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Temporomandibular joint osteoarthritis (TMJ OA) leads to permanent cartilage destruction, jaw dysfunction, and compromises the quality of life. However, the pathological mechanisms governing TMJ OA are poorly understood. Unlike appendicular articular cartilage, the TMJ has two distinct functions as the synovial joint of the craniofacial complex and also as the site for endochondral jaw bone growth. The established dogma of endochondral bone ossification is that hypertrophic chondrocytes undergo apoptosis, while invading vasculature with osteoprogenitors replace cartilage with bone. However, contemporary murine genetic studies support the direct differentiation of chondrocytes into osteoblasts and osteocytes in the TMJ. Here we sought to characterize putative vasculature and cartilage to bone transdifferentiation using healthy and diseased TMJ tissues from miniature pigs and humans. During endochondral ossification, the presence of fully formed vasculature expressing CD31(+) endothelial cells and alpha-SMA(+) vascular smooth muscle cells were detected within all cellular zones in growing miniature pigs. Arterial, endothelial, venous, angiogenic, and mural cell markers were significantly upregulated in miniature pig TMJ tissues relative to donor matched knee meniscus fibrocartilage tissue. Upon surgically creating TMJ OA in miniature pigs, we discovered increased vasculature and putative chondrocyte to osteoblast transformation dually marked by COL2 and BSP or RUNX2 within the vascular bundles. Pathological human TMJ tissues also exhibited increased vasculature, while isolated diseased human TMJ cells exhibited marked increased in vasculature markers relative to control 293T cells. Our study provides evidence to suggest that the TMJ in higher order species are in fact vascularized. There have been no reports of cartilage to bone transdifferentiation or vasculature in human-relevant TMJ OA large animal models or in human TMJ tissues and cells. Therefore, these findings may potentially alter the clinical management of TMJ OA by defining new drugs that target angiogenesis or block the cartilage to bone transformation.
引用
收藏
页码:4445 / 4461
页数:17
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