Perspective: Advancing the science regarding temporomandibular disorders.

This Special Issue was initiated in response to the call for improved research by the National Academies of Sciences, Engineering, and Medicine (NASEM) (United States) Consensus Study Report on Temporomandibular Disorders (TMDs), a set of putatively localized musculoskeletal conditions. In this Special Issue, the importance of systems biology for TMDs emerges from each of three separate publications. The importance of systems biology to patients is anchored in two domains-laboratory research and clinical observation.

Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity.

Osteoarthritis is a degenerative joint disease that causes pain, degradation, and dysfunction. Excessive canonical Wnt signaling in osteoarthritis contributes to chondrocyte phenotypic instability and loss of cartilage homeostasis; however, the regulatory niche is unknown. Using the temporomandibular joint as a model in multiple species, we identify Lgr5-expressing secretory cells as forming a Wnt inhibitory niche that instruct Wnt-inactive chondroprogenitors to form the nascent synovial joint and regulate chondrocyte lineage and identity.

Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic TMJ osteoarthritis rabbit model.

Objective: The temporomandibular joint (TMJ) is anatomically comprised of the mandibular condylar cartilage (CC) lined with fibrocartilaginous superficial zone and is crucial for eating and dental occlusion. TMJ osteoarthritis (OA) leads to pain, joint dysfunction and permanent loss of cartilage tissue. However, there are no drugs clinically available that ameliorate OA and little is known about global profiles of genes that contribute to TMJ OA.

Biomaterials for recruiting and activating endogenous stem cells in situ tissue regeneration.

Over the past two decades in situ tissue engineering has emerged as a new approach where biomaterials are used to harness the body's own stem/progenitor cells to regenerate diseased or injured tissue. Immunomodulatory biomaterials are designed to promote a regenerative environment, recruit resident stem cells to diseased or injured tissue sites, and direct them towards tissue regeneration. This review explores advances gathered from in vitro and in vivo studies on in situ tissue regenerative therapies.

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

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.

Extracellular matrix turnover and inflammation in chemically-induced TMJ arthritis mouse models.

The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies.

Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells.

Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine known to promote embryonic stem cells survival, is robustly adipogenic and induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. In vitro, Ptn stimulated human adipose tissue derived ASCs to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides.

Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury.

Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage.

Periodontal Ligament and Alveolar Bone in Health and Adaptation: Tooth Movement.

The periodontal ligament (PDL) and alveolar bone are two critical tissues for understanding orthodontic tooth movement. The current literature is replete with descriptive studies of multiple cell types and their matrices in the PDL and alveolar bone, but is deficient with how stem/progenitor cells differentiate into PDL and alveolar bone cells. Can one type of orthodontic force with a specific magnitude and frequency activate osteoblasts, whereas another force type activates osteoclasts? This chapter will discuss the biology of not only mature cells and their matrices in the periodontal ligament and alveolar bone, but also stem/progenitor cells that differentiate into fibroblasts, osteoblasts and osteoclasts.

Engineered nasal cartilage by cell homing: a model for augmentative and reconstructive rhinoplasty.

Background: Current augmentative and reconstructive rhinoplasties use auto logous tissue grafts or synthetic bioinert materials to repair nasal trauma or attain an aesthetic shape. Autologous grafts are associated with donor-site trauma and morbidity. Synthetic materials are widely used but often yield an unnatural appearance and are prone to infection or dislocation.

Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo.

Dentin and dental pulp regeneration by the patient's endogenous cells.

The goal of regenerative endodontics is to restore the functions of the dental pulp-dentin complex. Two approaches are being applied toward dental pulp-dentin regeneration: cell transplantation and cell homing. The majority of previous approaches are based on cell transplantation by delivering cultivated cells toward dental pulp or dentin regeneration.

Musculoskeletal tissue engineering by endogenous stem/progenitor cells.

From its inception, tissue engineering has had three tenets: cells, biomaterial scaffolds and signaling molecules. Among the triad, cells are the center piece, because cells are the building blocks of tissues. For decades, cell therapies have focused on the procurement, manipulation and delivery of healthy cells for the treatment of diseases or trauma.

Characterization of dental pulp defect and repair in a canine model.

Purpose: To explore a relationship between the size of pulp chamber perforation and reparative dentin formation in a canine model.

Methods: Pulp defects were created in the pulp chambers of maxillary and mandibular premolars (N = 64) in 17 healthy mongrel dogs in three different sizes (diameter/depth: 1/1, 2/1, and 2/2 mm3) with sterile round burs under general anesthesia. The perforations were immediately capped with hard-setting calcium hydroxide (CH) in the control group or sealed with Teflon membrane (TM) in the experimental group, followed by restoration with reinforced zinc oxide eugenol cement in vivo.

Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis.

The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn(-/0)Fmod(-/-)).

Fibromodulin-deficient mice reveal dual functions for fibromodulin in regulating dental tissue and alveolar bone formation.

The extracellular matrix of newborn, 7- and 21-day-old fibromodulin-deficient (Fmod KO) mice was compared with age-matched wild-type (WT) mice. Western blotting of proteins from 21-day-old WT mice revealed that the molecular weight of Fmod is smaller in dental tissues (approx. 40 kDa) compared to alveolar bone extracts (approx.

Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo.

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice.

Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures are unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture from wild-type (Wt) mice.

Mice deficient in biglycan and fibromodulin as a model for temporomandibular joint osteoarthritis.

The temporomandibular joint (TMJ) within the craniofacial complex is unique. In humans, the TMJ can become diseased resulting in severe and disabling pain. There are no cures for TMJ disease at this time.

Regulation, regulatory activities, and function of biglycan.

Biglycan is a member of the small leucine repeat proteoglycan family (SLRP). The biglycan gene is located on the X chromosome. Based on the amino acid sequence, the protein core of biglycan can be divided into six distinct domains: (1) a signal sequence, (2) a propeptide region, (3) a N-terminal glycosaminoglycan attachment region, (4) a cysteine loop, followed by (5) a leucine- rich repeat region domain (that makes up over 66% of the core protein), and (6) a final cysteine loop.