title: Unilateral anterior crossbite induces aberrant mineral deposition in degenerative temporomandibular cartilage in rats.
abstract: OBJECTIVE
  To investigate whether mechanical stress induces mineral deposits that contribute to matrix degradation at the onset of osteoarthritis (OA) in temporomandibular joint (TMJ) cartilage.
  
  
  METHODS
  Female Spraguee-Dawley rats were subjected to an unilateral anterior crossbite (UAC) procedure. Histology, electron microscopy, and energy dispersive spectrometer (EDS) were used to examine cartilage matrix structures and composition of mineral deposit in the affected TMJ cartilage. Protein and/or RNA expression of phenotypic markers and mineralization modulators and matrix degradation was analyzed by immunohistochemistry and/or real-time PCR. Synthetic basic calcium phosphate (BCP) and calcium pyrophosphate dehydrate (CPPD) crystals were used to stimulate ATDC5 cells for their impact on cell differentiation and gene expression.
  
  
  RESULTS
  Fragmented and disorganized collagen fibers, expanded fibrous spaces, and enhancement of matrix vesicle production and mineral deposition were observed in matrices surrounding hypertrophic chondrocytes in cartilage as early as 2-weeks post-UAC and exacerbated with time. The mineral deposits in TMJ cartilage at 12- and 20-weeks post-UAC had Ca/P ratios of 1.42 and 1.44, which are similar to the ratios for BCP. The expression of mineralization inhibitors, NPP1, ANK, CD73, and Matrix gla protein (MGP) was decreased from 2 to 8 weeks post-UAC, so were the chondrogenic markers, Col-2, Col-X and aggrecan. In contrast, the expression of tissue-nonspecific alkaline phosphatase (TNAP) and MMP13 was increased 4-weeks post-UAC. Treating ADTC5 cells with BCP crystals increased MMPs and ADAMTS5 expression, but reduced matrix production in a time-dependent manner.
  
  
  CONCLUSIONS
  UAC induces deposition of BCP-like minerals in osteoarthritic cartilage, which can stimulate matrix degradation by promoting the expression of cartilage-degrading enzymes to facilitate OA progression.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, USA; Department of Medicine, University of California San Francisco, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China. Electronic address: mqwang@fmmu.edu.cn.
authors.forename: M
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000378:metabolism / Q000494:pharmacology; D002131:Calcium Pyrophosphate / Q000378:metabolism / Q000494:pharmacology; D002357:Cartilage Diseases / Q000209:etiology* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002805:Chondrocalcinosis / Q000209:etiology* / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D008310:Malocclusion / Q000150:complications*; D008854:Microscopy, Electron; D017207:Rats, Sprague-Dawley; D013704:Temporomandibular Joint / Q000378:metabolism / Q000648:ultrastructure; D013705:Temporomandibular Joint Disorders / Q000209:etiology* / Q000473:pathology
chemical_list: D002130:Calcium Phosphates; C020243:calcium phosphate; D002131:Calcium Pyrophosphate
keywords: BCP; CPPD; Calcium-crystal; Osteoarthritis (OA); Temporomandibular joint (TMJ)