Bone matrix-directed chondrogenesis of muscle in vitro.

Bone matrix is the largely collagenous residue of demineralized bone. Experimental data demonstrate that a substance, which is acid-stable during demineralization, occurs as a part of bone matrix, and that it is capable of stimulating the redifferentiation of skeletal muscle into cartilage. Reproducibility of redifferentiation is high and all cells derived from embryonic mesoderm appear competent to yield cartilage. This effect is highly significant to the developmental biology of musculoskeletal tissues, as muscle and cartilage arise from a similar embryonic origin. With regard to the embryonic limb as a model system, it appears that both muscle and cartilage progenitor cells do not have rigidly-defined developmental programs, and that this is a result of their origin from a common pool of embryonic mesoderm. This pool originates as embryonic mesenchyme long before any evidence of limb development can be detected. It is proposed that the active component of bone matrix, termed "bone morphogenetic protein (BMP)," acts upon a tissue whose developmental program is not stabilized, or has been experimentally destabilized (by injury), to augment and sustain syntheses of cartilage extracellular matrix. The use of bone matrix, and active substances derived from it, suggests that differentiation is not irreversible. Hard tissue growth and repair may occur via recruitment of competent responding cells from a variety of nonchondrogenic sources, provided that the extracellular milieu (i.e., presence of BMP) is supportive.