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Spotlight on Tendon: Its Novel Role in Long Bone Growth and Rickets‐Caused Osteosclerosis
Author(s) -
Li Hui,
Jing Yan,
Ma Chi,
Wang Zheng,
Feng Jian Q.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05320
Subject(s) - osteosclerosis , rickets , hypophosphatemia , hypophosphatemic rickets , dmp1 , tendon , endochondral ossification , osteomalacia , medicine , phex , osteocyte , osteoclast , anatomy , bone cell , pathology , osteoblast , biology , osteoporosis , vitamin d and neurology , cartilage , immunology , biochemistry , virus , receptor , viral matrix protein , in vitro
It has been known for many years that tendon‐attached bone is rough and bump, and that patients with hypophosphatemic rickets (such as DMP1 mutations) develop osteosclerosis in the tendon‐attached area. The goal of this study was to test whether tendon directly forms bone and how hypophosphatemia initiates the onset of osteosclerosis in a Dmp1 KO mouse (a hypophosphatemic rickets model) using cell lineage tracing and multiple imaging techniques. METHODS We generated a chondrocyte tracing mouse line (Col 10a1‐Cre;R26R tomato) and a tendon tracing mouse line (Scx‐CreERT2;R26R tomato) with and without a Dmp1 KO background, plus a high Pi rescue diet treatment for seven weeks. RESULTS Our key findings were: 1) the non‐tendon attached bone cells were negative in both tracing lines; 2) cells in the tendon‐attached bone were Scx+ but Col X − ; 3). In the Dmp1 KO mice, tendon‐attached bone volume sharply increased, in which there were more EdU+ bone cells (i.e., more cell proliferation) with high expression levels of bone markers such as Runx2 and β‐catenin; and 4) a high Pi diet greatly improved the above phenotypes. CONCLUSION Tendon (an avascular tissue) directly forms bone cells in the tendon‐bone joint area, which is rough and porous compared to non‐tendon attached bones. Osteosclerosis in Dmp1 KO (a hypophosphatemia rickets model) is caused by accelerated cell transdifferentiation from tendon to bone due to hypophosphatemia. Support or Funding Information U.S. National Institutes of Health grants to J.Q.F. (R01DE025014 and DE025659)